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 56 12 74 24 52 25 58 73 36 29 13 54 6 43 15 39 71
Homogentisic Acid Oxidase Deficiency 56 52 25 58 73
Alcaptonuria 12 24 52 25
Aku 56 52 25 73
Alkaptonuric Ochronosis 52 71
Ochronosis, Hereditary 52 71
Homogentisic Acidura 52 25
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:

56
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:

24
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 56 203500
KEGG 36 H00163
MeSH 43 D000474
NCIt 49 C84546
SNOMED-CT 67 360381004
ICD10 32 E70.29
MESH via Orphanet 44 C537862 D000474
ICD10 via Orphanet 33 E70.2
UMLS via Orphanet 72 C0002066 C2931645
Orphanet 58 ORPHA56
MedGen 41 C0002066
UMLS 71 C0002066 C1444199 C2931645

Summaries for Alkaptonuria

OMIM : 56 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)

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 heart, kidney and prostate, 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.

Genetics Home Reference : 25 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.

NIH Rare Diseases : 52 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 : 73 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 : 74 Alkaptonuria is a rare inherited genetic disorder 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 164)
# Related Disease Score Top Affiliating Genes
1 ochronosis 32.6 TYR MRAP HPD HGD
2 abdominal obesity-metabolic syndrome 1 30.3 PAH HGD FAH
3 phenylketonuria 30.0 PRODH PAH HPD
4 histidinemia 29.6 PRODH NIT2
5 tyrosinemia 29.2 TYR TAT PAH HPD HGD GSTZ1
6 inherited metabolic disorder 11.6
7 exogenous ochronosis 11.2
8 arthropathy 10.8
9 autosomal recessive disease 10.6
10 disorder of tyrosine metabolism 10.4
11 prostate calculus 10.3 HPD HGD
12 aortic valve disease 2 10.3
13 back pain 10.3
14 lower urinary tract calculus 10.3 HPD HGD
15 spondyloarthropathy 10.3
16 spondyloarthropathy 1 10.3
17 renal cell carcinoma, nonpapillary 10.3
18 carotid stenosis 10.3
19 aneurysm 10.3
20 cerebral aneurysms 10.3
21 spondylosis 10.3
22 keratopathy 10.3
23 osteoarthritis 10.3
24 amyloidosis 10.3
25 kidney disease 10.2
26 arthritis 10.2
27 visual epilepsy 10.2
28 47,xyy 10.2
29 seizure disorder 10.2
30 central neurocytoma 10.2
31 enthesopathy 10.2
32 heart valve disease 10.2
33 chondrocalcinosis 10.1
34 inflammatory spondylopathy 10.1
35 prostatitis 10.1
36 spondylitis 10.1
37 neuroblastoma 10.1
38 purine-pyrimidine metabolic disorder 10.1 PRODH MOCOS
39 urate oxidase, pseudogene 10.1
40 immune deficiency disease 10.1
41 mycosis fungoides 10.1
42 heart disease 10.1
43 hypogonadism 10.1
44 astrocytoma 10.1
45 pituitary adenoma 10.1
46 adenoma 10.1
47 juvenile pilocytic astrocytoma 10.1
48 cleft lip 10.1
49 48,xyyy 10.1
50 urea cycle disorder 10.0 PRODH PAH FAH

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 arthralgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002829
4 hearing abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0000364
5 joint dislocation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001373
6 irregular hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007400
7 abnormality of vision 58 31 hallmark (90%) Very frequent (99-80%) HP:0000504
8 joint swelling 58 31 hallmark (90%) Very frequent (99-80%) HP:0001386
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 reduced bone mineral density 58 31 occasional (7.5%) Occasional (29-5%) HP:0004349
24 myocardial infarction 58 31 occasional (7.5%) Occasional (29-5%) HP:0001658
25 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
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 abnormality of metabolism/homeostasis 31 HP:0001939
30 abnormal heart valve morphology 58 Frequent (79-30%)
31 abnormality of skin pigmentation 58 Very frequent (99-80%)
32 back pain 31 HP:0003418
33 abnormality of the eye 58 Very frequent (99-80%)
34 abnormality of the urinary system 31 HP:0000079
35 vertebral fusion 31 HP:0002948
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:

56
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

UMLS symptoms related to Alkaptonuria:


back pain

MGI Mouse Phenotypes related to Alkaptonuria:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.77 ARL13B FAH GSTZ1 HGD HPD LIG3
2 renal/urinary system MP:0005367 9.17 ARL13B FAH GSTZ1 HGD HPD PAH

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, Phase 3 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 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
2 Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria Unknown status NCT01390077 Phase 2, Phase 3 Nitisinone
3 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
4 Long-Term Clinical Trial of Nitisinone in Alkaptonuria Completed NCT00107783 Phase 2 Nitisinone (NTBC)
5 Clinical, Biochemical, and Molecular Investigations Into Alkaptonuria Recruiting NCT00005909
6 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. Recruiting NCT04196959
7 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
Heart, Kidney, Prostate, Skin, Eye, Bone, Liver

Publications for Alkaptonuria

Articles related to Alkaptonuria:

(show top 50) (show all 842)
# Title Authors PMID Year
1
The molecular basis of alkaptonuria. 6 54 24 56 61
8782815 1996
2
Mutational analysis of the HGO gene in Finnish alkaptonuria patients. 54 61 56 6
10594001 1999
3
Allelic heterogeneity of alkaptonuria in Central Europe. 56 6 61 54
10482952 1999
4
Molecular defects in alkaptonuria. 6 56 54 61
9154114 1997
5
Alkaptonuria caused by compound heterozygote mutations. 6 61 56
12872815 2003
6
Natural history of alkaptonuria. 54 61 56 24
12501223 2002
7
Structural and functional analysis of mutations in alkaptonuria. 56 6 61
11001939 2000
8
Novel mutations in the homogentisate-1,2-dioxygenase gene identified in Slovak patients with alkaptonuria. 56 6 61
10970188 2000
9
Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients. 61 56 6
9529363 1998
10
Effects of ascorbic acid in alkaptonuria: alterations in benzoquinone acetic acid and an ontogenic effect in infancy. 61 24 56
2771520 1989
11
Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria. 54 61 56
19862842 2009
12
Molecular diagnosis of alkaptonuria mutation by analysis of homogentisate 1,2 dioxygenase mRNA from urine and blood. 61 6 54
9674916 1998
13
The human gene for alkaptonuria (AKU) maps to chromosome 3q. 54 61 56
8188241 1994
14
OCHRONOSIS FROM QUINACRINE (ATABRINE). 24 56
14065956 1963
15
Use of nitisinone in patients with alkaptonuria. 54 24 61
15931605 2005
16
Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain. 54 24 61
15529343 2004
17
Alkaptonuria 6 61
20301627 2003
18
Rapid detection methods for five HGO gene mutations causing alkaptonuria. 61 54 24
12630963 2003
19
High frequency of alkaptonuria in Slovakia: evidence for the appearance of multiple mutations in HGO involving different mutational hot spots. 24 61 54
11017803 2000
20
Increased urolithiasis in patients with alkaptonuria in childhood. 56 61
10945668 2000
21
A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria. 61 56
10083729 1999
22
Effects of ascorbic acid and low-protein diet in alkaptonuria. 61 56
9809834 1998
23
Are we ready to try to cure alkaptonuria? 61 56
9529368 1998
24
aku, a mutation of the mouse homologous to human alkaptonuria, maps to chromosome 16. 61 56
8188247 1994
25
Homozygosity mapping of the gene for alkaptonuria to chromosome 3q2. 56 61
8252048 1993
26
Bilateral hip and bilateral knee arthroplasties in a patient with ochronotic arthropathy. 61 56
2270175 1990
27
Ochronosis and alkaptonuria: report of a new case with calcified aortic valve stenosis. 61 56
2316305 1990
28
Neonatal severe primary hyperparathyroidism and alkaptonuria in a boy born to related parents with familial hypocalciuric hypercalcemia. 61 56
6543841 1984
29
Alkaptonuria and ochronosis. A survey and 5 cases. 61 56
6862457 1983
30
Alkaptonuria in the Trencín District of Czechoslovakia. 61 56
263435 1978
31
[Alkaptonuria, ochronotic arthropathy and aortic stenosis]. 56 61
5038994 1972
32
Thirteen cases of alkaptonuria from one family tree with special reference to osteo-arthrosis alkaptonurica. 61 56
13848727 1960
33
Alkaptonuria and ochronosis. 56 61
13849350 1959
34
Sir Archibald Garrod's inborn errors of metabolism. II. Alkaptonuria. 61 56
13533390 1958
35
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy. 61 24
25804398 2016
36
First report of a deletion encompassing an entire exon in the homogentisate 1,2-dioxygenase gene causing alkaptonuria. 61 24
25233259 2014
37
Aortic stenosis and vascular calcifications in alkaptonuria. 61 24
22100375 2012
38
A 3-year randomized therapeutic trial of nitisinone in alkaptonuria. 61 24
21620748 2011
39
Musculoskeletal findings and disability in alkaptonuria. 24 61
16981292 2006
40
Arthroplasty for ochronotic arthritis: no failure of 11 replacements in 3 patients followed 6-12 years. 24 61
15260431 2004
41
Alkaptonuria, ochronosis, and ochronotic arthropathy. 24 61
14978662 2004
42
Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation. 61 24
12359141 2002
43
Alkaptonuria in the Dominican Republic: identification of the founder AKU mutation and further evidence of mutation hot spots in the HGO gene. 24 61
12114497 2002
44
Alkaptonuria in Slovakia: thirty-two years of research on phenotype and genotype. 24 61
12051967 2002
45
NTBC and alkaptonuria. 24 61
9718357 1998
46
The human homogentisate 1,2-dioxygenase (HGO) gene. 24 61
9244427 1997
47
Exogenous ochronosis. 56
8463477 1993
48
Novel phenylketonuria mutation detected by analysis of ectopically transcribed phenylalanine hydroxylase mRNA from lymphoblast. 6
1360590 1992
49
Prostatic and renal stones and unilateral obstruction of the urinary tract caused by ochronosis. 56
1727353 1992
50
Rapidly progressive hip osteoarthrosis--an unusual presentation of ochronosis. 56
2667832 1989

Variations for Alkaptonuria

ClinVar genetic disease variations for Alkaptonuria:

6 (show top 50) (show all 124) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HGD NM_000187.4(HGD):c.189G>T (p.Arg63Ser)SNV Pathogenic 437464 rs1390061303 3:120389367-120389367 3:120670520-120670520
2 HGD NM_000187.4(HGD):c.1078G>C (p.Gly360Arg)SNV Pathogenic 640206 3:120352104-120352104 3:120633257-120633257
3 HGD NM_000187.4(HGD):c.651_652del (p.Ala218Glnfs)deletion Pathogenic 643931 3:120363288-120363289 3:120644441-120644442
4 HGD NM_000187.4(HGD):c.291G>A (p.Trp97Ter)SNV Pathogenic 855743 3:120371490-120371490 3:120652643-120652643
5 HGD NM_000187.4(HGD):c.990G>T (p.Arg330Ser)SNV Pathogenic 3167 rs120074171 3:120357318-120357318 3:120638471-120638471
6 HGD NM_000187.4(HGD):c.481G>A (p.Gly161Arg)SNV Pathogenic 3168 rs28941783 3:120365888-120365888 3:120647041-120647041
7 HGD NM_000187.4(HGD):c.457dup (p.Asp153fs)duplication Pathogenic 3169 rs397515346 3:120366735-120366736 3:120647888-120647889
8 HGD NM_000187.4(HGD):c.16-1G>ASNV Pathogenic 3170 rs397515347 3:120394711-120394711 3:120675864-120675864
9 HGD NM_000187.4(HGD):c.175del (p.Ser59fs)deletion Pathogenic 3171 rs397515517 3:120393749-120393749 3:120674902-120674902
10 HGD NM_000187.4(HGD):c.1112A>G (p.His371Arg)SNV Pathogenic 3172 rs120074172 3:120352070-120352070 3:120633223-120633223
11 HGD NM_000187.4(HGD):c.1102A>G (p.Met368Val)SNV Pathogenic 3173 rs120074173 3:120352080-120352080 3:120633233-120633233
12 HGD NM_000187.4(HGD):c.808G>A (p.Gly270Arg)SNV Pathogenic 3175 rs120074174 3:120360507-120360507 3:120641660-120641660
13 HGD NM_000187.4(HGD):c.1111dup (p.His371fs)duplication Pathogenic 65573 rs397515516 3:120352070-120352071 3:120633223-120633224
14 HGD NM_000187.4(HGD):c.140C>T (p.Ser47Leu)SNV Pathogenic 65574 rs369517993 3:120393784-120393784 3:120674937-120674937
15 HGD NM_000187.4(HGD):c.360T>G (p.Cys120Trp)SNV Pathogenic 65578 rs149165166 3:120369695-120369695 3:120650848-120650848
16 HGD NM_000187.4(HGD):c.16-272_87+305deldeletion Pathogenic 156275 rs1553721650 3:120394334-120394982 3:120675487-120676135
17 HGD NC_000003.12:g.(?_120647857)_(120647931_?)deldeletion Pathogenic 830678 3:120366704-120366778
18 HGD NM_000187.4(HGD):c.1039C>T (p.Arg347Ter)SNV Pathogenic 850435 3:120352143-120352143 3:120633296-120633296
19 HGD NM_000187.4(HGD):c.688C>T (p.Pro230Ser)SNV Pathogenic 3165 rs28942100 3:120363252-120363252 3:120644405-120644405
20 HGD NM_000187.4(HGD):c.1017_1019delinsTA (p.Met339fs)indel Pathogenic 371197 rs1057517081 3:120352163-120352165 3:120633316-120633318
21 HGD NM_000187.4(HGD):c.899T>G (p.Val300Gly)SNV Pathogenic/Likely pathogenic 3166 rs120074170 3:120357409-120357409 3:120638562-120638562
22 HGD NM_000187.4(HGD):c.680T>C (p.Phe227Ser)SNV Likely pathogenic 836287 3:120363260-120363260 3:120644413-120644413
23 HGD NM_000187.4(HGD):c.11T>A (p.Leu4Ter)SNV Likely pathogenic 188717 rs786204422 3:120400948-120400948 3:120682101-120682101
24 HGD NM_000187.4(HGD):c.1336T>C (p.Ter446Arg)SNV Likely pathogenic 188735 rs143370662 3:120347229-120347229 3:120628382-120628382
25 HGD NM_000187.4(HGD):c.674G>A (p.Arg225His)SNV Likely pathogenic 189173 rs562853291 3:120363266-120363266 3:120644419-120644419
26 HGD NM_000187.3(HGD):c.652delG (p.Ala218Profs)deletion Likely pathogenic 189061 rs786204662 3:120363288-120363288 3:120644441-120644441
27 HGD NM_000187.4(HGD):c.365C>T (p.Ala122Val)SNV Likely pathogenic 188865 rs544956641 3:120369690-120369690 3:120650843-120650843
28 HGD NM_000187.4(HGD):c.342+1G>TSNV Likely pathogenic 189127 rs397515518 3:120371438-120371438 3:120652591-120652591
29 HGD NM_000187.4(HGD):c.342+1G>ASNV Likely pathogenic 65577 rs397515518 3:120371438-120371438 3:120652591-120652591
30 HGD NM_000187.4(HGD):c.753C>T (p.Gly251=)SNV Likely pathogenic 867232 3:120363187-120363187 3:120644340-120644340
31 HGD NC_000003.12:g.(?_120633127)_(120633348_?)deldeletion Likely pathogenic 645876 3:120351974-120352195 3:120633127-120633348
32 HGD NM_000187.4(HGD):c.879+1G>ASNV Likely pathogenic 556131 rs1553716979 3:120360435-120360435 3:120641588-120641588
33 HGD NM_000187.4(HGD):c.970dup (p.Val324fs)duplication Likely pathogenic 371566 rs34214309 3:120357337-120357338 3:120638490-120638491
34 HGD NM_000187.4(HGD):c.956del (p.Pro319fs)deletion Likely pathogenic 371206 rs1057517089 3:120357352-120357352 3:120638505-120638505
35 HGD NM_000187.4(HGD):c.781dup (p.Ser261fs)duplication Likely pathogenic 371624 rs1057517418 3:120360533-120360534 3:120641686-120641687
36 HGD NM_000187.4(HGD):c.649+2T>CSNV Likely pathogenic 370198 rs1057516307 3:120365112-120365112 3:120646265-120646265
37 HGD NM_000187.4(HGD):c.390del (p.Ala132fs)deletion Likely pathogenic 370253 rs1057516352 3:120369665-120369665 3:120650818-120650818
38 HGD NM_000187.4(HGD):c.376_377del (p.Lys126fs)deletion Likely pathogenic 371063 rs1057516976 3:120369678-120369679 3:120650831-120650832
39 HGD NM_000187.4(HGD):c.346del (p.Leu116fs)deletion Likely pathogenic 370977 rs1057516911 3:120369709-120369709 3:120650862-120650862
40 HGD NM_000187.4(HGD):c.339_342+2deldeletion Likely pathogenic 370654 rs1057516662 3:120371437-120371442 3:120652590-120652595
41 HGD NM_000187.4(HGD):c.179G>A (p.Trp60Ter)SNV Likely pathogenic 370411 rs1057516467 3:120389377-120389377 3:120670530-120670530
42 HGD NM_000187.4(HGD):c.177-1G>ASNV Likely pathogenic 371563 rs1057517370 3:120389380-120389380 3:120670533-120670533
43 HGD NM_000187.4(HGD):c.158G>A (p.Arg53Gln)SNV Likely pathogenic 370939 rs200808744 3:120393766-120393766 3:120674919-120674919
44 HGD NM_000187.4(HGD):c.58del (p.Arg20fs)deletion Likely pathogenic 370893 rs1057516849 3:120394668-120394668 3:120675821-120675821
45 HGD NM_000187.4(HGD):c.31_32delinsATT (p.Gly11fs)indel Likely pathogenic 370267 rs1057516362 3:120394694-120394695 3:120675847-120675848
46 HGD NM_000187.4(HGD):c.15+1G>ASNV Likely pathogenic 370545 rs552207335 3:120400943-120400943 3:120682096-120682096
47 HGD NM_000187.4(HGD):c.3G>C (p.Met1Ile)SNV Likely pathogenic 370258 rs1057516355 3:120400956-120400956 3:120682109-120682109
48 HGD NM_000187.4(HGD):c.409del (p.Leu137fs)deletion Likely pathogenic 370989 rs1057516921 3:120369646-120369646 3:120650799-120650799
49 HGD NM_000187.4(HGD):c.1201G>C (p.Glu401Gln)SNV Likely pathogenic 371502 rs767159114 3:120347364-120347364 3:120628517-120628517
50 HGD NM_000187.4(HGD):c.1188+1G>TSNV Likely pathogenic 370979 rs760206323 3:120351993-120351993 3:120633146-120633146

UniProtKB/Swiss-Prot genetic disease variations for Alkaptonuria:

73 (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
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

Pathways related to Alkaptonuria according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.65 TYR TAT PRODH PAH NIT2 MOCS1
2
Show member pathways
13.33 TYR TAT PRODH PAH HPD HGD
3
Show member pathways
11.59 TAT PRODH PAH HPD HGD GSTZ1
4
Show member pathways
11.05 TYR TAT PAH HPD HGD GSTZ1
5
Show member pathways
10.79 PAH MOCS1 MOCOS
6
Show member pathways
10.73 TAT HPD

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 9.65 TYR TAT PAH NIT2 MOCS1 MOCOS
2 9+0 non-motile cilium GO:0097731 8.62 SMO ARL13B

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.8 TYR PRODH PAH HPD HGD
2 aromatic amino acid family metabolic process GO:0009072 9.55 TAT PAH HPD GSTZ1 FAH
3 cellular amino acid metabolic process GO:0006520 9.43 TAT HGD
4 left/right axis specification GO:0070986 9.37 SMO ARL13B
5 tyrosine catabolic process GO:0006572 9.35 TAT HPD HGD GSTZ1 FAH
6 molybdopterin cofactor biosynthetic process GO:0032324 9.32 MOCS1 MOCOS
7 Mo-molybdopterin cofactor biosynthetic process GO:0006777 9.26 MOCS1 MOCOS
8 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 oxidoreductase activity GO:0016491 9.35 TYR PRODH PAH HPD HGD
2 catalytic activity GO:0003824 9.1 TAT PAH MOCS1 MOCOS GSTZ1 FAH

Sources for Alkaptonuria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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