AKU
MCID: ALK013
MIFTS: 58

Alkaptonuria (AKU)

Categories: Bone diseases, Eye diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases, Skin diseases

Aliases & Classifications for Alkaptonuria

MalaCards integrated aliases for Alkaptonuria:

Name: Alkaptonuria 57 12 73 25 20 43 58 72 36 29 13 54 6 44 15 39 70
Homogentisic Acid Oxidase Deficiency 57 20 43 58 72
Alcaptonuria 12 25 20 43
Aku 57 20 43 72
Alkaptonuric Ochronosis 20 70
Ochronosis, Hereditary 20 70
Homogentisic Acidura 20 43
Homogentisate 1,2-Dioxygenase Deficiency 12
Deficiency of Homogentisicase 12
Hereditary Ochronosis 58

Characteristics:

Orphanet epidemiological data:

58
alkaptonuria
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Worldwide),1-9/1000000 (Europe),1-9/1000000 (France),1-9/100000 (Slovakia); Age of onset: Adult,Infancy; Age of death: normal life expectancy;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
urine turns dark on standing and alkalinization
joint symptoms begin in third or fourth decade
affects 1 in 250,000 to 1 million people worldwide


HPO:

31
alkaptonuria:
Inheritance autosomal recessive inheritance


GeneReviews:

25
Penetrance Elevated urinary hga and ochronotic arthritis occur in all individuals who are homozygous or compound heterozygous for pathogenic variants in hgd.

Classifications:

Orphanet: 58  
Rare eye diseases
Rare skin diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:9270
OMIM® 57 203500
KEGG 36 H00163
MeSH 44 D000474
NCIt 50 C84546
SNOMED-CT 67 24250001
ICD10 32 E70.29
MESH via Orphanet 45 C537862 D000474
ICD10 via Orphanet 33 E70.2
UMLS via Orphanet 71 C0002066 C2931645
Orphanet 58 ORPHA56
MedGen 41 C0002066
UMLS 70 C0002066 C1444199 C2931645

Summaries for Alkaptonuria

OMIM® : 57 Alkaptonuria is an autosomal recessive metabolic disorder characterized by accumulation of homogentisic acid, leading to darkened urine, pigmentation of connective tissue (ochronosis), joint and spine arthritis, and destruction of the cardiac valves (summary by Vilboux et al., 2009). Alkaptonuria enjoys the historic distinction of being one of the first conditions in which mendelian recessive inheritance was proposed (by Garrod, 1902, on the suggestion of Bateson) and of being 1 of the 4 conditions in the charter group of inborn errors of metabolism. The manifestations are urine that turns dark on standing and alkalinization, black ochronotic pigmentation of cartilage and collagenous tissues, and arthritis, especially characteristic in the spine. (203500) (Updated 20-May-2021)

MalaCards based summary : Alkaptonuria, also known as homogentisic acid oxidase deficiency, is related to ochronosis and abdominal obesity-metabolic syndrome 1, and has symptoms including back pain An important gene associated with Alkaptonuria is HGD (Homogentisate 1,2-Dioxygenase), and among its related pathways/superpathways are Tyrosine metabolism and Metabolism. The drugs Nitisinone and Tyrosine have been mentioned in the context of this disorder. Affiliated tissues include eye, prostate and bone, and related phenotypes are joint stiffness and aminoaciduria

Disease Ontology : 12 An amino acid metabolic disorder that involves phenylalanine and tyrosine metabolism with the accumulation of homogentisic acid, a toxic tyrosine byproduct.

MedlinePlus Genetics : 43 Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones.

GARD : 20 Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. The three major features of alkaptonuria are the presence of dark urine, ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, and arthritis of the spine and larger joints. Ochronosis starts after age 30 and arthritis in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones. Alkaptonuria is caused by mutations in the HGD gene. It is inherited in an autosomal recessive fashion. There is still no cure for this disease. Treatment includes the management of joint pain, physical and occupational therapy, joint replacements and surgery when needed.

KEGG : 36 Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase that leads to the widespread deposition of polymeric homogentisic acid, and clinical symptoms from degeneration of joints and the aortic valve.

UniProtKB/Swiss-Prot : 72 Alkaptonuria: An autosomal recessive error of metabolism characterized by an increase in the level of homogentisic acid. The clinical manifestations are urine that turns dark on standing and alkalinization, black ochronotic pigmentation of cartilage and collagenous tissues, and spine arthritis.

Wikipedia : 73 Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the HGD gene for the... more...

GeneReviews: NBK1454

Related Diseases for Alkaptonuria

Diseases related to Alkaptonuria via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 173)
# Related Disease Score Top Affiliating Genes
1 ochronosis 32.2 HPD HGD FAH CRYAA
2 abdominal obesity-metabolic syndrome 1 30.1 PAH HGD FAH
3 tyrosinemia 29.7 TAT PAH HPD HGD GSTZ1 FAH
4 phenylketonuria 29.4 PRODH PAH HPD HGD ADSL
5 histidinemia 29.4 PRODH NIT2 ADSL
6 inherited metabolic disorder 11.0
7 exogenous ochronosis 10.9
8 arthropathy 10.6
9 autosomal recessive disease 10.5
10 disorder of tyrosine metabolism 10.3
11 aortic valve disease 2 10.2
12 spondyloarthropathy 10.2
13 aortic valve disease 1 10.2
14 spondylosis 10.1
15 keratopathy 10.1
16 osteoarthritis 10.1
17 amyloidosis 10.1
18 back pain 10.1
19 spondyloarthropathy 1 10.1
20 renal cell carcinoma, nonpapillary 10.1
21 carotid stenosis 10.1
22 aneurysm 10.1
23 cerebral aneurysms 10.1
24 kidney disease 10.1
25 hawkinsinuria 10.1 TAT HPD FAH
26 physical disorder 10.0 PRODH CRYAA ARL13B
27 parkinsonism 10.0
28 enthesopathy 10.0
29 heart valve disease 10.0
30 hyperprolinemia, type i 10.0 PRODH ADSL
31 47,xyy 10.0
32 seizure disorder 10.0
33 tyrosinemia, type ii 10.0 TAT HPD HGD FAH
34 chondrocalcinosis 10.0
35 inflammatory spondylopathy 10.0
36 prostatitis 10.0
37 spondylitis 10.0
38 neuroblastoma 10.0
39 tyrosinemia, type iii 10.0 TAT HPD HGD FAH
40 hyperphenylalaninemia, bh4-deficient, a 10.0 PAH MOCS1
41 hyperprolinemia, type ii 10.0 PRODH MOCS2
42 3-methylcrotonyl-coa carboxylase deficiency 9.9 PRODH ADSL
43 central neurocytoma 9.9
44 arteries, anomalies of 9.9
45 osteoporosis 9.9
46 nephrolithiasis, calcium oxalate 9.9
47 dowling-degos disease 1 9.9
48 cystinuria 9.9
49 osteogenic sarcoma 9.9
50 tyrosinosis 9.9

Graphical network of the top 20 diseases related to Alkaptonuria:



Diseases related to Alkaptonuria

Symptoms & Phenotypes for Alkaptonuria

Human phenotypes related to Alkaptonuria:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
2 aminoaciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003355
3 hearing abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0000364
4 arthralgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002829
5 irregular hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007400
6 abnormality of vision 58 31 hallmark (90%) Very frequent (99-80%) HP:0000504
7 joint swelling 58 31 hallmark (90%) Very frequent (99-80%) HP:0001386
8 joint dislocation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001373
9 osteoarthritis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002758
10 blue sclerae 58 31 hallmark (90%) Very frequent (99-80%) HP:0000592
11 coronary artery calcification 58 31 hallmark (90%) Very frequent (99-80%) HP:0001717
12 intervertebral disk calcification 58 31 hallmark (90%) Very frequent (99-80%) HP:0005645
13 calcification of cartilage 58 31 hallmark (90%) Very frequent (99-80%) HP:0100593
14 abnormality of the nail 58 31 frequent (33%) Frequent (79-30%) HP:0001597
15 mitral valve calcification 58 31 frequent (33%) Frequent (79-30%) HP:0004382
16 nephrolithiasis 58 31 frequent (33%) Frequent (79-30%) HP:0000787
17 abnormality of the nose 58 31 frequent (33%) Frequent (79-30%) HP:0000366
18 prostatitis 58 31 frequent (33%) Frequent (79-30%) HP:0000024
19 aortic valve calcification 58 31 frequent (33%) Frequent (79-30%) HP:0004380
20 thickened achilles tendon 58 31 frequent (33%) Frequent (79-30%) HP:0004690
21 tendon rupture 58 31 frequent (33%) Frequent (79-30%) HP:0100550
22 cartilage destruction 58 31 frequent (33%) Frequent (79-30%) HP:0100773
23 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
24 reduced bone mineral density 58 31 occasional (7.5%) Occasional (29-5%) HP:0004349
25 myocardial infarction 58 31 occasional (7.5%) Occasional (29-5%) HP:0001658
26 atherosclerosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002621
27 arthritis 58 31 Very frequent (99-80%) HP:0001369
28 kyphosis 31 HP:0002808
29 abnormal heart valve morphology 58 Frequent (79-30%)
30 back pain 31 HP:0003418
31 abnormality of the eye 58 Very frequent (99-80%)
32 abnormality of the urinary system 31 HP:0000079
33 vertebral fusion 31 HP:0002948
34 abnormality of metabolism/homeostasis 31 HP:0001939
35 abnormality of skin pigmentation 58 Very frequent (99-80%)
36 aortic aneurysm 31 HP:0004942
37 abnormality of the ear 31 HP:0000598
38 arthropathy 31 HP:0003040
39 intervertebral disc degeneration 31 HP:0008419
40 pigmentation of the sclera 31 HP:0007832
41 growth abnormality 31 HP:0001507

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
kyphosis
back pain
degeneration of intervertebral disks
fusion of vertebral bodies
decreased lumbar flexion

Skeletal Feet:
thickened achilles tendon

Skeletal:
chronic joint pain
ochronotic pigmentation of fibrous tissues including cartilage, tendons, ligaments
ochronotic arthritis
ochronotic arthropathy

Head And Neck Ears:
pigmentation of the ear cartilage

Genitourinary Kidneys:
urolithiasis

Cardiovascular Heart:
mitral valve calcification
coronary artery calcification
aortic valve calcification
aortic dilatation

Head And Neck Eyes:
pigmentation of the sclera

Growth Height:
height loss secondary to spinal changes

Genitourinary Internal Genitalia Male:
ochronotic prostate stones

Laboratory Abnormalities:
increased plasma homogentisic acid (hga)
increased urinary hga
decreased liver homogentisate 1,2-dioxygenase activity

Clinical features from OMIM®:

203500 (Updated 20-May-2021)

UMLS symptoms related to Alkaptonuria:


back pain

MGI Mouse Phenotypes related to Alkaptonuria:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 9.23 ARL13B CASR FAH GSTZ1 HGD HPD

Drugs & Therapeutics for Alkaptonuria

Drugs for Alkaptonuria (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nitisinone Approved, Investigational Phase 2 104206-65-7 115355
2
Tyrosine Approved, Investigational, Nutraceutical Phase 2 60-18-4 6057

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria Unknown status NCT01390077 Phase 2, Phase 3 Nitisinone
2 An International, Multicentre, Randomised, Evaluator-blind, No-treatment Controlled, Parallel-group Study to Assess the Efficacy and Safety of Once Daily Nitisinone in Patients With Alkaptonuria After 12 Months of Treatment, Followed by an Additional 36 Month Treatment Period. Unknown status NCT01916382 Phase 3 Nitisinone
3 Long-Term Clinical Trial of Nitisinone in Alkaptonuria Completed NCT00107783 Phase 2 Nitisinone (NTBC)
4 An International, Multicentre, Randomised, Open-label, No-treatment Controlled, Parallel-group, Dose-response Study to Investigate the Effect of Once Daily Nitisinone on 24-hour Urinary Homogentisic Acid Excretion in Patients With Alkaptonuria After 4 Weeks Treatment. Completed NCT01828463 Phase 2 Nitisinone
5 Clinical, Biochemical, and Molecular Investigations Into Alkaptonuria Recruiting NCT00005909
6 Questionnaire Follow=up Study Sonia 2 Recruiting NCT04510142
7 An Acceptability Study to Evaluate the Adherence, Tolerance and Metabolic Control of Patients With Tyrosinaemia, When Using TYR Sphere (a Food for Special Medical Purposes (FSMP)) as Part of Dietary Management. Active, not recruiting NCT04196959
8 Determining Individualised Gait Modification Strategies to Reduce Knee Joint Moments in Alkaptonuria Patients Using Real-time Feedback Not yet recruiting NCT04142671

Search NIH Clinical Center for Alkaptonuria

Cochrane evidence based reviews: alkaptonuria

Genetic Tests for Alkaptonuria

Genetic tests related to Alkaptonuria:

# Genetic test Affiliating Genes
1 Alkaptonuria 29 HGD

Anatomical Context for Alkaptonuria

MalaCards organs/tissues related to Alkaptonuria:

40
Eye, Prostate, Bone, Heart, Kidney, Liver, Skin

Publications for Alkaptonuria

Articles related to Alkaptonuria:

(show top 50) (show all 888)
# Title Authors PMID Year
1
Natural history of alkaptonuria. 57 54 6 25 61
12501223 2002
2
The molecular basis of alkaptonuria. 61 6 57 54 25
8782815 1996
3
Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria. 54 61 6 57
19862842 2009
4
Mutational analysis of the HGO gene in Finnish alkaptonuria patients. 54 61 6 57
10594001 1999
5
Allelic heterogeneity of alkaptonuria in Central Europe. 54 61 57 6
10482952 1999
6
Molecular defects in alkaptonuria. 61 54 6 57
9154114 1997
7
Alkaptonuria caused by compound heterozygote mutations. 61 57 6
12872815 2003
8
Structural and functional analysis of mutations in alkaptonuria. 61 6 57
11001939 2000
9
Novel mutations in the homogentisate-1,2-dioxygenase gene identified in Slovak patients with alkaptonuria. 61 6 57
10970188 2000
10
Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients. 61 57 6
9529363 1998
11
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy. 25 61 6
25804398 2016
12
First report of a deletion encompassing an entire exon in the homogentisate 1,2-dioxygenase gene causing alkaptonuria. 6 25 61
25233259 2014
13
Alkaptonuria in the Dominican Republic: identification of the founder AKU mutation and further evidence of mutation hot spots in the HGO gene. 6 25 61
12114497 2002
14
Alkaptonuria in Slovakia: thirty-two years of research on phenotype and genotype. 25 6 61
12051967 2002
15
Effects of ascorbic acid in alkaptonuria: alterations in benzoquinone acetic acid and an ontogenic effect in infancy. 61 25 57
2771520 1989
16
A novel missense HGD gene mutation, K57N, in a patient with alkaptonuria. 54 61 6
19306858 2009
17
R58fs mutation in the HGD gene in a family with alkaptonuria in the UAE. 54 61 6
18945288 2009
18
Ochronotic rheumatism in Algeria: clinical, radiological, biological and molecular studies--a case study of 14 patients in 11 families. 61 6 54
16085442 2006
19
Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from central Asia and was spread throughout Europe and Anatolia by human migrations. 6 61 54
12872836 2003
20
Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene. 6 61 54
10340975 1999
21
Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene (HGO). 61 54 6
10205262 1999
22
Molecular diagnosis of alkaptonuria mutation by analysis of homogentisate 1,2 dioxygenase mRNA from urine and blood. 61 54 6
9674916 1998
23
The human gene for alkaptonuria (AKU) maps to chromosome 3q. 57 54 61
8188241 1994
24
OCHRONOSIS FROM QUINACRINE (ATABRINE). 25 57
14065956 1963
25
Alkaptonuria: a disease with dark brown urine. 61 6
27026014 2016
26
A Founder Effect for the HGD G360R Mutation in Italy: Implications for a Regional Screening of Alkaptonuria. 6 61
26960557 2016
27
Analysis of HGD Gene Mutations in Patients with Alkaptonuria from the United Kingdom: Identification of Novel Mutations. 61 6
25681086 2015
28
First report of HGD mutations in a Chinese with alkaptonuria. 6 61
23353776 2013
29
Novel mutations in the homogentisate 1,2 dioxygenase gene identified in Jordanian patients with alkaptonuria. 61 6
21437689 2012
30
Identification of 11 Novel Homogentisate 1,2 Dioxygenase Variants in Alkaptonuria Patients and Establishment of a Novel LOVD-Based HGD Mutation Database. 6 61
23430897 2012
31
An update on molecular genetics of Alkaptonuria (AKU). 61 6
21720873 2011
32
Familiar ochronotic arthropathy-caused by a gene mutation traced three hundred years. 6 61
20462779 2010
33
Three-generational alkaptonuria in a non-consanguineous family. 6 61
19096913 2008
34
Use of nitisinone in patients with alkaptonuria. 61 54 25
15931605 2005
35
Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain. 61 25 54
15529343 2004
36
Rapid detection methods for five HGO gene mutations causing alkaptonuria. 54 25 61
12630963 2003
37
High frequency of alkaptonuria in Slovakia: evidence for the appearance of multiple mutations in HGO involving different mutational hot spots. 61 25 54
11017803 2000
38
Increased urolithiasis in patients with alkaptonuria in childhood. 57 61
10945668 2000
39
Alkaptonuria in Italy: polymorphic haplotype background, mutational profile, and description of four novel mutations in the homogentisate 1,2-dioxygenase gene. 61 6
10819641 2000
40
Sequence analysis of the homogentisate 1,2 dioxygenase gene in a family affected by alkaptonuria. 6 61
10465119 1999
41
A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria. 57 61
10083729 1999
42
Effects of ascorbic acid and low-protein diet in alkaptonuria. 61 57
9809834 1998
43
Are we ready to try to cure alkaptonuria? 61 57
9529368 1998
44
A novel point mutation associated with alkaptonuria. 6 61
9630082 1998
45
aku, a mutation of the mouse homologous to human alkaptonuria, maps to chromosome 16. 57 61
8188247 1994
46
Homozygosity mapping of the gene for alkaptonuria to chromosome 3q2. 57 61
8252048 1993
47
Bilateral hip and bilateral knee arthroplasties in a patient with ochronotic arthropathy. 61 57
2270175 1990
48
Ochronosis and alkaptonuria: report of a new case with calcified aortic valve stenosis. 57 61
2316305 1990
49
Neonatal severe primary hyperparathyroidism and alkaptonuria in a boy born to related parents with familial hypocalciuric hypercalcemia. 61 57
6543841 1984
50
Alkaptonuria and ochronosis. A survey and 5 cases. 61 57
6862457 1983

Variations for Alkaptonuria

ClinVar genetic disease variations for Alkaptonuria:

6 (show top 50) (show all 136)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HGD NM_000187.4(HGD):c.360T>G (p.Cys120Trp) SNV Pathogenic 65578 rs149165166 GRCh37: 3:120369695-120369695
GRCh38: 3:120650848-120650848
2 HGD NM_000187.4(HGD):c.1111dup (p.His371fs) Duplication Pathogenic 65573 rs397515516 GRCh37: 3:120352070-120352071
GRCh38: 3:120633223-120633224
3 HGD NM_000187.4(HGD):c.140C>T (p.Ser47Leu) SNV Pathogenic 65574 rs369517993 GRCh37: 3:120393784-120393784
GRCh38: 3:120674937-120674937
4 HGD NM_000187.4(HGD):c.16-272_87+305del Deletion Pathogenic 156275 rs1553721650 GRCh37: 3:120394334-120394982
GRCh38: 3:120675487-120676135
5 HGD NM_000187.4(HGD):c.808G>A (p.Gly270Arg) SNV Pathogenic 3175 rs120074174 GRCh37: 3:120360507-120360507
GRCh38: 3:120641660-120641660
6 HGD NM_000187.4(HGD):c.1102A>G (p.Met368Val) SNV Pathogenic 3173 rs120074173 GRCh37: 3:120352080-120352080
GRCh38: 3:120633233-120633233
7 HGD NM_000187.4(HGD):c.1112A>G (p.His371Arg) SNV Pathogenic 3172 rs120074172 GRCh37: 3:120352070-120352070
GRCh38: 3:120633223-120633223
8 HGD NM_000187.4(HGD):c.175del (p.Ser59fs) Deletion Pathogenic 3171 rs397515517 GRCh37: 3:120393749-120393749
GRCh38: 3:120674902-120674902
9 HGD NM_000187.4(HGD):c.16-1G>A SNV Pathogenic 3170 rs397515347 GRCh37: 3:120394711-120394711
GRCh38: 3:120675864-120675864
10 HGD NM_000187.4(HGD):c.457dup (p.Asp153fs) Duplication Pathogenic 3169 rs397515346 GRCh37: 3:120366735-120366736
GRCh38: 3:120647888-120647889
11 HGD NM_000187.4(HGD):c.481G>A (p.Gly161Arg) SNV Pathogenic 3168 rs28941783 GRCh37: 3:120365888-120365888
GRCh38: 3:120647041-120647041
12 HGD NM_000187.4(HGD):c.990G>T (p.Arg330Ser) SNV Pathogenic 3167 rs120074171 GRCh37: 3:120357318-120357318
GRCh38: 3:120638471-120638471
13 HGD NM_000187.4(HGD):c.688C>T (p.Pro230Ser) SNV Pathogenic 3165 rs28942100 GRCh37: 3:120363252-120363252
GRCh38: 3:120644405-120644405
14 HGD NM_000187.4(HGD):c.1017_1019delinsTA (p.Met339fs) Indel Pathogenic 371197 rs1057517081 GRCh37: 3:120352163-120352165
GRCh38: 3:120633316-120633318
15 HGD NM_000187.4(HGD):c.189G>T (p.Arg63Ser) SNV Pathogenic 437464 rs1390061303 GRCh37: 3:120389367-120389367
GRCh38: 3:120670520-120670520
16 HGD NM_000187.4(HGD):c.1078G>C (p.Gly360Arg) SNV Pathogenic 640206 rs368717991 GRCh37: 3:120352104-120352104
GRCh38: 3:120633257-120633257
17 HGD NM_000187.4(HGD):c.651_652del (p.Ala218Glnfs) Deletion Pathogenic 643931 rs786204662 GRCh37: 3:120363288-120363289
GRCh38: 3:120644441-120644442
18 HGD NC_000003.12:g.(?_120647857)_(120647931_?)del Deletion Pathogenic 830678 GRCh37: 3:120366704-120366778
GRCh38:
19 HGD NM_000187.4(HGD):c.1039C>T (p.Arg347Ter) SNV Pathogenic 850435 GRCh37: 3:120352143-120352143
GRCh38: 3:120633296-120633296
20 HGD NM_000187.4(HGD):c.291G>A (p.Trp97Ter) SNV Pathogenic 855743 GRCh37: 3:120371490-120371490
GRCh38: 3:120652643-120652643
21 HGD NM_000187.4(HGD):c.1A>G (p.Met1Val) SNV Pathogenic 929477 GRCh37: 3:120400958-120400958
GRCh38: 3:120682111-120682111
22 HGD NM_000187.4(HGD):c.502G>A (p.Glu168Lys) SNV Pathogenic 944660 GRCh37: 3:120365867-120365867
GRCh38: 3:120647020-120647020
23 HGD NM_000187.4(HGD):c.469+1G>C SNV Pathogenic 967202 GRCh37: 3:120366723-120366723
GRCh38: 3:120647876-120647876
24 HGD NM_000187.4(HGD):c.774+6_774+10del Microsatellite Pathogenic 1032245 GRCh37: 3:120363156-120363160
GRCh38: 3:120644309-120644313
25 HGD NM_000187.4(HGD):c.899T>G (p.Val300Gly) SNV Pathogenic/Likely pathogenic 3166 rs120074170 GRCh37: 3:120357409-120357409
GRCh38: 3:120638562-120638562
26 HGD NM_000187.4(HGD):c.365C>T (p.Ala122Val) SNV Pathogenic/Likely pathogenic 188865 rs544956641 GRCh37: 3:120369690-120369690
GRCh38: 3:120650843-120650843
27 HGD NM_000187.4(HGD):c.1336T>C (p.Ter446Arg) SNV Likely pathogenic 188735 rs143370662 GRCh37: 3:120347229-120347229
GRCh38: 3:120628382-120628382
28 HGD NM_000187.4(HGD):c.11T>A (p.Leu4Ter) SNV Likely pathogenic 188717 rs786204422 GRCh37: 3:120400948-120400948
GRCh38: 3:120682101-120682101
29 HGD NM_000187.4(HGD):c.342+1G>A SNV Likely pathogenic 65577 rs397515518 GRCh37: 3:120371438-120371438
GRCh38: 3:120652591-120652591
30 HGD NM_000187.3(HGD):c.652delG (p.Ala218Profs) Deletion Likely pathogenic 189061 rs786204662 GRCh37: 3:120363288-120363288
GRCh38: 3:120644441-120644441
31 HGD NM_000187.4(HGD):c.342+1G>T SNV Likely pathogenic 189127 rs397515518 GRCh37: 3:120371438-120371438
GRCh38: 3:120652591-120652591
32 HGD NM_000187.4(HGD):c.674G>A (p.Arg225His) SNV Likely pathogenic 189173 rs562853291 GRCh37: 3:120363266-120363266
GRCh38: 3:120644419-120644419
33 HGD NM_000187.4(HGD):c.390del (p.Ala132fs) Deletion Likely pathogenic 370253 rs1057516352 GRCh37: 3:120369665-120369665
GRCh38: 3:120650818-120650818
34 HGD NM_000187.4(HGD):c.1201G>C (p.Glu401Gln) SNV Likely pathogenic 371502 rs767159114 GRCh37: 3:120347364-120347364
GRCh38: 3:120628517-120628517
35 HGD NM_000187.4(HGD):c.970dup (p.Val324fs) Duplication Likely pathogenic 371566 rs34214309 GRCh37: 3:120357337-120357338
GRCh38: 3:120638490-120638491
36 HGD NM_000187.4(HGD):c.179G>A (p.Trp60Ter) SNV Likely pathogenic 370411 rs1057516467 GRCh37: 3:120389377-120389377
GRCh38: 3:120670530-120670530
37 HGD NM_000187.4(HGD):c.1188+1G>T SNV Likely pathogenic 370979 rs760206323 GRCh37: 3:120351993-120351993
GRCh38: 3:120633146-120633146
38 HGD NM_000187.4(HGD):c.31_32delinsATT (p.Gly11fs) Indel Likely pathogenic 370267 rs1057516362 GRCh37: 3:120394694-120394695
GRCh38: 3:120675847-120675848
39 HGD NM_000187.4(HGD):c.15+1G>A SNV Likely pathogenic 370545 rs552207335 GRCh37: 3:120400943-120400943
GRCh38: 3:120682096-120682096
40 HGD NM_000187.4(HGD):c.956del (p.Pro319fs) Deletion Likely pathogenic 371206 rs1057517089 GRCh37: 3:120357352-120357352
GRCh38: 3:120638505-120638505
41 HGD NM_000187.4(HGD):c.781dup (p.Ser261fs) Duplication Likely pathogenic 371624 rs1057517418 GRCh37: 3:120360533-120360534
GRCh38: 3:120641686-120641687
42 HGD NM_000187.4(HGD):c.409del (p.Leu137fs) Deletion Likely pathogenic 370989 rs1057516921 GRCh37: 3:120369646-120369646
GRCh38: 3:120650799-120650799
43 HGD NM_000187.4(HGD):c.1064dup (p.Gly356fs) Duplication Likely pathogenic 370890 rs1057516847 GRCh37: 3:120352117-120352118
GRCh38: 3:120633270-120633271
44 HGD NM_000187.4(HGD):c.346del (p.Leu116fs) Deletion Likely pathogenic 370977 rs1057516911 GRCh37: 3:120369709-120369709
GRCh38: 3:120650862-120650862
45 HGD NM_000187.4(HGD):c.58del (p.Arg20fs) Deletion Likely pathogenic 370893 rs1057516849 GRCh37: 3:120394668-120394668
GRCh38: 3:120675821-120675821
46 HGD NM_000187.4(HGD):c.649+2T>C SNV Likely pathogenic 370198 rs1057516307 GRCh37: 3:120365112-120365112
GRCh38: 3:120646265-120646265
47 HGD NM_000187.4(HGD):c.177-1G>A SNV Likely pathogenic 371563 rs1057517370 GRCh37: 3:120389380-120389380
GRCh38: 3:120670533-120670533
48 HGD NM_000187.4(HGD):c.376_377del (p.Lys126fs) Deletion Likely pathogenic 371063 rs1057516976 GRCh37: 3:120369678-120369679
GRCh38: 3:120650831-120650832
49 HGD NM_000187.4(HGD):c.3G>C (p.Met1Ile) SNV Likely pathogenic 370258 rs1057516355 GRCh37: 3:120400956-120400956
GRCh38: 3:120682109-120682109
50 HGD NM_000187.4(HGD):c.158G>A (p.Arg53Gln) SNV Likely pathogenic 370939 rs200808744 GRCh37: 3:120393766-120393766
GRCh38: 3:120674919-120674919

UniProtKB/Swiss-Prot genetic disease variations for Alkaptonuria:

72 (show top 50) (show all 68)
# Symbol AA change Variation ID SNP ID
1 HGD p.Glu42Ala VAR_005272 rs373921680
2 HGD p.Trp60Gly VAR_005273
3 HGD p.Tyr62Cys VAR_005274 rs117458485
4 HGD p.Trp97Gly VAR_005275
5 HGD p.Ala122Asp VAR_005276
6 HGD p.Asp153Gly VAR_005277 rs775274569
7 HGD p.Gly161Arg VAR_005278 rs28941783
8 HGD p.Ser189Ile VAR_005279
9 HGD p.Ile216Thr VAR_005280 rs767201131
10 HGD p.Arg225His VAR_005281 rs562853291
11 HGD p.Phe227Ser VAR_005282
12 HGD p.Pro230Ser VAR_005283 rs28942100
13 HGD p.Pro230Thr VAR_005284
14 HGD p.Asp291Glu VAR_005285 rs754428438
15 HGD p.Val300Gly VAR_005286 rs120074170
16 HGD p.Met368Val VAR_005287 rs120074173
17 HGD p.Arg330Ser VAR_008744 rs120074171
18 HGD p.His371Arg VAR_008745 rs120074172
19 HGD p.Leu25Pro VAR_009618
20 HGD p.Glu168Lys VAR_009619 rs375283568
21 HGD p.Gly270Arg VAR_009620 rs120074174
22 HGD p.Glu3Ala VAR_073076 rs200412910
23 HGD p.Glu13Lys VAR_073077 rs145875224
24 HGD p.Asp18Asn VAR_073078
25 HGD p.Gln33Arg VAR_073079
26 HGD p.Leu44Phe VAR_073080 rs104924617
27 HGD p.Arg53Gln VAR_073081 rs200808744
28 HGD p.Leu61Pro VAR_073082 rs132465441
29 HGD p.Phe73Leu VAR_073083
30 HGD p.Pro92Thr VAR_073084
31 HGD p.Trp97Arg VAR_073085
32 HGD p.Gly115Arg VAR_073086 rs755734596
33 HGD p.Leu116Pro VAR_073087 rs569846003
34 HGD p.Cys120Phe VAR_073088 rs752153829
35 HGD p.Cys120Trp VAR_073089 rs149165166
36 HGD p.Ala122Val VAR_073090 rs544956641
37 HGD p.Gly123Ala VAR_073091 rs374473331
38 HGD p.Gly123Arg VAR_073092 rs564979861
39 HGD p.Leu137Pro VAR_073093
40 HGD p.Gly152Ala VAR_073094 rs155371793
41 HGD p.Pro158Leu VAR_073095 rs375396766
42 HGD p.Glu168Asp VAR_073096 rs780173554
43 HGD p.Phe169Leu VAR_073097 rs756134838
44 HGD p.Lys171Asn VAR_073098
45 HGD p.Glu178Gly VAR_073100
46 HGD p.Gln183Arg VAR_073101 rs134954305
47 HGD p.Arg187Gly VAR_073102 rs756255206
48 HGD p.Arg197Gly VAR_073103 rs141427973
49 HGD p.Gly217Trp VAR_073104
50 HGD p.Asn219Ser VAR_073105

Expression for Alkaptonuria

Search GEO for disease gene expression data for Alkaptonuria.

Pathways for Alkaptonuria

Pathways related to Alkaptonuria according to KEGG:

36
# Name Kegg Source Accession
1 Tyrosine metabolism hsa00350

GO Terms for Alkaptonuria

Cellular components related to Alkaptonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.73 TAT PAH NIT2 MOCS2 MOCS1 MOCOS
2 molybdopterin synthase complex GO:0019008 8.62 MOCS2 MOCS1

Biological processes related to Alkaptonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.58 PAH GSTZ1 CHIT1
2 aromatic amino acid family metabolic process GO:0009072 9.55 TAT PAH HPD GSTZ1 FAH
3 molybdopterin cofactor biosynthetic process GO:0032324 9.5 MOCS2 MOCS1 MOCOS
4 Mo-molybdopterin cofactor biosynthetic process GO:0006777 9.43 MOCS2 MOCS1 MOCOS
5 left/right axis specification GO:0070986 9.37 SMO ARL13B
6 tyrosine catabolic process GO:0006572 9.35 TAT HPD HGD GSTZ1 FAH
7 L-phenylalanine catabolic process GO:0006559 9.1 TAT PAH HPD HGD GSTZ1 FAH

Molecular functions related to Alkaptonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 9.33 MOCS1 MOCOS ADSL
2 catalytic activity GO:0003824 9.17 TAT PAH MOCS1 MOCOS GSTZ1 FAH
3 amino acid binding GO:0016597 8.96 TAT CASR

Sources for Alkaptonuria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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