HSAN2B
MCID: NRP018
MIFTS: 39

Neuropathy, Hereditary Sensory and Autonomic, Type Iib (HSAN2B)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

MalaCards integrated aliases for Neuropathy, Hereditary Sensory and Autonomic, Type Iib:

Name: Neuropathy, Hereditary Sensory and Autonomic, Type Iib 56 13 71
Hereditary Sensory and Autonomic Neuropathy Type Iib 12 73 29 6
Hsan2b 56 12 73
Hereditary Sensory and Autonomic Neuropathy Type 2b 12 15
Neuropathy, Sensory and Autonomic, Hereditary, Type Iib 39
Neuropathy, Hereditary Sensory and Autonomic, 2b 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in first or second decade


HPO:

31
neuropathy, hereditary sensory and autonomic, type iib:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset progressive


Classifications:



External Ids:

Disease Ontology 12 DOID:0070150
OMIM 56 613115
OMIM Phenotypic Series 56 PS162400
MeSH 43 D009477
MedGen 41 C2751092
UMLS 71 C2751092

Summaries for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

UniProtKB/Swiss-Prot : 73 Neuropathy, hereditary sensory and autonomic, 2B: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2B is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation. Onset occurs in the first or second decade, with impaired nociception and progressive mutilating ulceration of the hands and feet with osteomyelitis and acroosteolysis. Amputations of the hands and feet are common. Autonomic dysfunction includes hyperhidrosis, urinary incontinence, and slow pupillary light response.

MalaCards based summary : Neuropathy, Hereditary Sensory and Autonomic, Type Iib, also known as hereditary sensory and autonomic neuropathy type iib, is related to neuropathy, hereditary sensory and autonomic, type iia and neurogenic arthropathy. An important gene associated with Neuropathy, Hereditary Sensory and Autonomic, Type Iib is RETREG1 (Reticulophagy Regulator 1), and among its related pathways/superpathways are Factors involved in megakaryocyte development and platelet production and Diuretics Pathway, Pharmacodynamics. Affiliated tissues include eye, bone and skin, and related phenotypes are spasticity and areflexia

Disease Ontology : 12 A hereditary sensory and autonomic neuropathy type 2 characterized by early childhood onset of distal sensory impairment that has material basis in homozygous mutation in the FAM134B gene on chromosome 5p15.

OMIM : 56 Hereditary sensory and autonomic neuropathy type IIB is an autosomal recessive neurologic disorder characterized by early childhood onset of distal sensory impairment usually resulting in ulceration and associated with variable autonomic features, such as hyperhidrosis and urinary incontinence. Some patients may show impaired gait (summary by Ilgaz Aydinlar et al., 2014). HSAN2A (201300) is caused by mutation in the HSN2 isoform of the WNK1 gene (WNK1/HSN2; see 605232). For a discussion of genetic heterogeneity of HSAN, see HSAN1 (162400). (613115)

Related Diseases for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Diseases in the Autosomal Dominant Hereditary Sensory and Autonomic Neuropathy family:

Neuropathy, Hereditary Sensory and Autonomic, Type Ia Neuropathy, Hereditary Sensory and Autonomic, Type Iia
Neuropathy, Hereditary Sensory and Autonomic, Type Iii Neuropathy, Hereditary Sensory and Autonomic, Type V
Neuropathy, Hereditary Sensory and Autonomic, Type Iib Neuropathy, Hereditary Sensory and Autonomic, Type Ic
Neuropathy, Hereditary Sensory and Autonomic, Type Vi Neuropathy, Hereditary Sensory and Autonomic, Type Vii
Neuropathy, Hereditary Sensory and Autonomic, Type Viii Hereditary Sensory and Autonomic Neuropathy Type 1
Autosomal Recessive Hereditary Sensory and Autonomic Neuropathy

Diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)
# Related Disease Score Top Affiliating Genes
1 neuropathy, hereditary sensory and autonomic, type iia 30.1 WNK1 STK39 SNRPA SCN9A RTN4 RETREG1
2 neurogenic arthropathy 10.3 SCN9A NAA50
3 autonomic dysfunction 10.3 SCN9A RETREG1
4 neuropathy, hereditary sensory and autonomic, type ia 10.3 WNK1 NAA50
5 neuropathy, hereditary sensory and autonomic, type viii 10.2 RETREG1 NAA50
6 hereditary sensory and autonomic neuropathy type 1 10.1 RETREG1 NAA50
7 autonomic nervous system disease 10.1 SCN9A NAA50
8 renal tubular transport disease 10.1 WNK1 STK39
9 diabetes mellitus, insulin-dependent, 24 10.0 WNK1 DACT1
10 diabetes mellitus, insulin-dependent, 20 10.0 WNK1 DACT1
11 hemoglobin lepore-beta-thalassemia syndrome 10.0 HBD HBB
12 hemoglobin c disease 10.0 HBD HBB
13 hemoglobin d disease 10.0 HBD HBB
14 gitelman syndrome 10.0 WNK1 STK39
15 hemoglobin e disease 10.0 HBD HBB
16 malignant essential hypertension 10.0 HBD HBB
17 fetal hemoglobin quantitative trait locus 1 9.9 HBD HBB
18 sickle cell disease 9.9 HBD HBB
19 neuropathy, hereditary sensory and autonomic, type v 9.9 WNK1 RETREG1 NAA50 KIF1A
20 neuropathy 9.8 WNK1 SCN9A RETREG1 KIF1A
21 autonomic neuropathy 9.8 WNK1 SCN9A RETREG1 KIF1A
22 hemoglobin h disease 9.7 HBD HBB
23 charcot-marie-tooth disease, axonal, type 2e 9.6 RETREG1 NAA50 KIF1A
24 hereditary sensory neuropathy 9.6 WNK1 SCN9A RETREG1 NAA50 KIF1A
25 charcot-marie-tooth disease 9.6 WNK1 SCN9A RETREG1 NAA50 KIF1A

Graphical network of the top 20 diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib:



Diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Symptoms & Phenotypes for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Human phenotypes related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 HP:0001257
2 areflexia 31 HP:0001284
3 osteomyelitis 31 HP:0002754
4 hyporeflexia 31 HP:0001265
5 urinary incontinence 31 HP:0000020
6 peripheral axonal neuropathy 31 HP:0003477
7 episodic hyperhidrosis 31 HP:0001069
8 autoamputation of digits 31 HP:0007460
9 osteolytic defects of the phalanges of the hand 31 HP:0009771
10 acral ulceration 31 HP:0006121

Symptoms via clinical synopsis from OMIM:

56
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
axonal neuropathy
impaired sensation in distal extremities, particularly pain and temperature (lower limbs more affected than upper limbs)
spasticity (2 families)
more
Genitourinary Bladder:
urinary incontinence

Skeletal Feet:
acroosteolysis
acral ulceration leading to autoamputation of digits

Head And Neck Eyes:
impaired pupillary response to light

Skeletal:
osteomyelitis

Skeletal Hands:
acroosteolysis
acral ulceration leading to autoamputation of digits

Skin Nails Hair Skin:
hyperhidrosis, episodic
ulcerations of distal extremities

Muscle Soft Tissue:
muscle weakness, distal and proximal, lower limbs (1 family)

Clinical features from OMIM:

613115

Drugs & Therapeutics for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Search Clinical Trials , NIH Clinical Center for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Genetic Tests for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Genetic tests related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib:

# Genetic test Affiliating Genes
1 Hereditary Sensory and Autonomic Neuropathy Type Iib 29 RETREG1

Anatomical Context for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

MalaCards organs/tissues related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib:

40
Eye, Bone, Skin

Publications for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Articles related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib:

# Title Authors PMID Year
1
Mutation in FAM134B causing hereditary sensory neuropathy with spasticity in a Turkish family. 56 6
24327336 2014
2
Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. 56 6
19838196 2009
3
Hereditary Sensory and Autonomic Neuropathy Type II 61 6
21089229 2010

Variations for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

ClinVar genetic disease variations for Neuropathy, Hereditary Sensory and Autonomic, Type Iib:

6 (show all 50) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RETREG1 NM_001034850.2(RETREG1):c.926C>G (p.Ser309Ter)SNV Pathogenic 328 rs137852739 5:16477845-16477845 5:16477736-16477736
2 RETREG1 FAM134B, 2-BP DEL, 17CTdeletion Pathogenic 329
3 RETREG1 NM_001034850.2(RETREG1):c.433C>T (p.Gln145Ter)SNV Pathogenic 330 rs137852737 5:16565897-16565897 5:16565788-16565788
4 RETREG1 FAM134B, IVS7DS, T-C, +2SNV Pathogenic 331
5 RETREG1 NM_001034850.2(RETREG1):c.826del (p.Ser276fs)deletion Conflicting interpretations of pathogenicity 203444 rs886037748 5:16478190-16478190 5:16478081-16478081
6 RETREG1 NM_001034850.2(RETREG1):c.380G>A (p.Arg127His)SNV Uncertain significance 379338 rs200871433 5:16572152-16572152 5:16572043-16572043
7 RETREG1 duplication Uncertain significance 470687 5:16474721-16481113
8 RETREG1 NM_001034850.2(RETREG1):c.953C>T (p.Thr318Ile)SNV Uncertain significance 352688 rs368457852 5:16477818-16477818 5:16477709-16477709
9 RETREG1 NM_001034850.2(RETREG1):c.1013C>T (p.Pro338Leu)SNV Uncertain significance 352687 rs886060395 5:16475331-16475331 5:16475222-16475222
10 RETREG1 NM_001034850.2(RETREG1):c.1426C>G (p.Gln476Glu)SNV Uncertain significance 470690 rs761585250 5:16474918-16474918 5:16474809-16474809
11 RETREG1 NM_001034850.2(RETREG1):c.1418C>G (p.Thr473Arg)SNV Uncertain significance 470689 rs1186811814 5:16474926-16474926 5:16474817-16474817
12 RETREG1 NM_001034850.2(RETREG1):c.466G>T (p.Val156Phe)SNV Uncertain significance 470693 rs758377163 5:16483574-16483574 5:16483465-16483465
13 RETREG1 NM_001034850.2(RETREG1):c.19C>G (p.Pro7Ala)SNV Uncertain significance 470691 rs532140281 5:16617062-16617062 5:16616953-16616953
14 RETREG1 NM_001034850.2(RETREG1):c.232T>C (p.Trp78Arg)SNV Uncertain significance 470692 rs746283428 5:16616849-16616849 5:16616740-16616740
15 RETREG1 NC_000005.9:g.(?_16616741)_(16617100_?)dupduplication Uncertain significance 538138 5:16616741-16617100 5:16616632-16616991
16 RETREG1 NM_001034850.2(RETREG1):c.1415T>C (p.Leu472Pro)SNV Uncertain significance 538133 rs1554014580 5:16474929-16474929 5:16474820-16474820
17 RETREG1 NM_001034850.2(RETREG1):c.555G>A (p.Met185Ile)SNV Uncertain significance 538128 rs780286920 5:16483485-16483485 5:16483376-16483376
18 RETREG1 NM_001034850.2(RETREG1):c.379C>G (p.Arg127Gly)SNV Uncertain significance 538119 rs78314670 5:16572153-16572153 5:16572044-16572044
19 RETREG1 NM_001034850.2(RETREG1):c.285C>G (p.Ser95Arg)SNV Uncertain significance 538131 rs1554026716 5:16616796-16616796 5:16616687-16616687
20 RETREG1 NM_001034850.2(RETREG1):c.210G>T (p.Trp70Cys)SNV Uncertain significance 538129 rs1554026745 5:16616871-16616871 5:16616762-16616762
21 RETREG1 NM_001034850.2(RETREG1):c.964T>C (p.Ser322Pro)SNV Uncertain significance 538134 rs1554014877 5:16477807-16477807 5:16477698-16477698
22 RETREG1 NM_001034850.2(RETREG1):c.457A>G (p.Ser153Gly)SNV Uncertain significance 538132 rs1554022467 5:16565873-16565873 5:16565764-16565764
23 RETREG1 NM_001034850.2(RETREG1):c.1378C>G (p.Gln460Glu)SNV Uncertain significance 538127 rs1554014585 5:16474966-16474966 5:16474857-16474857
24 RETREG1 NM_001034850.2(RETREG1):c.1207G>A (p.Asp403Asn)SNV Uncertain significance 538122 rs753136289 5:16475137-16475137 5:16475028-16475028
25 RETREG1 NM_001034850.2(RETREG1):c.1219C>T (p.His407Tyr)SNV Uncertain significance 538123 rs1554014624 5:16475125-16475125 5:16475016-16475016
26 RETREG1 NM_001034850.2(RETREG1):c.999T>A (p.Asp333Glu)SNV Uncertain significance 538130 rs771586180 5:16477772-16477772 5:16477663-16477663
27 RETREG1 NM_001034850.2(RETREG1):c.509G>C (p.Cys170Ser)SNV Uncertain significance 538120 rs779070741 5:16483531-16483531 5:16483422-16483422
28 RETREG1 NM_001034850.2(RETREG1):c.98C>A (p.Ser33Tyr)SNV Uncertain significance 538121 rs1326167901 5:16616983-16616983 5:16616874-16616874
29 RETREG1 NM_001034850.2(RETREG1):c.691C>T (p.Pro231Ser)SNV Uncertain significance 566340 rs1389950630 5:16479076-16479076 5:16478967-16478967
30 RETREG1 NM_001034850.2(RETREG1):c.687G>T (p.Leu229Phe)SNV Uncertain significance 568951 rs748217475 5:16479080-16479080 5:16478971-16478971
31 RETREG1 NM_001034850.2(RETREG1):c.1009C>T (p.Arg337Ter)SNV Uncertain significance 570577 rs750575538 5:16475335-16475335 5:16475226-16475226
32 RETREG1 NM_001034850.2(RETREG1):c.841A>G (p.Ser281Gly)SNV Uncertain significance 579164 rs1430719865 5:16478175-16478175 5:16478066-16478066
33 RETREG1 NM_001034850.2(RETREG1):c.1490A>G (p.His497Arg)SNV Uncertain significance 581538 rs746011053 5:16474854-16474854 5:16474745-16474745
34 RETREG1 NM_001034850.2(RETREG1):c.1169C>T (p.Thr390Met)SNV Uncertain significance 579199 rs374082497 5:16475175-16475175 5:16475066-16475066
35 RETREG1 NM_001034850.2(RETREG1):c.850G>T (p.Asp284Tyr)SNV Uncertain significance 583080 rs760751442 5:16478166-16478166 5:16478057-16478057
36 RETREG1 NM_001034850.2(RETREG1):c.68C>T (p.Ala23Val)SNV Uncertain significance 577840 rs1561141838 5:16617013-16617013 5:16616904-16616904
37 RETREG1 NM_001034850.2(RETREG1):c.743C>T (p.Ser248Leu)SNV Uncertain significance 645707 5:16479024-16479024 5:16478915-16478915
38 RETREG1 NM_001034850.2(RETREG1):c.691C>G (p.Pro231Ala)SNV Uncertain significance 648533 5:16479076-16479076 5:16478967-16478967
39 RETREG1 NM_001034850.2(RETREG1):c.614C>T (p.Thr205Ile)SNV Uncertain significance 660733 5:16481174-16481174 5:16481065-16481065
40 RETREG1 NM_001034850.2(RETREG1):c.428G>A (p.Gly143Asp)SNV Uncertain significance 658362 5:16565902-16565902 5:16565793-16565793
41 RETREG1 NM_001034850.2(RETREG1):c.364G>A (p.Val122Ile)SNV Uncertain significance 645729 5:16572168-16572168 5:16572059-16572059
42 RETREG1 NM_001034850.2(RETREG1):c.208T>A (p.Trp70Arg)SNV Uncertain significance 664214 5:16616873-16616873 5:16616764-16616764
43 RETREG1 NM_001034850.2(RETREG1):c.23A>G (p.Glu8Gly)SNV Uncertain significance 639309 5:16617058-16617058 5:16616949-16616949
44 RETREG1 NM_001034850.2(RETREG1):c.1026T>C (p.Val342=)SNV Likely benign 538135 rs765642043 5:16475318-16475318 5:16475209-16475209
45 RETREG1 NM_001034850.2(RETREG1):c.339A>G (p.Pro113=)SNV Likely benign 509333 rs372182225 5:16572193-16572193 5:16572084-16572084
46 RETREG1 NM_001034850.2(RETREG1):c.1110C>T (p.Pro370=)SNV Likely benign 470688 rs373322680 5:16475234-16475234 5:16475125-16475125
47 RETREG1 NM_001034850.2(RETREG1):c.1000+20G>TSNV Benign 518360 rs162850 5:16477751-16477751 5:16477642-16477642
48 RETREG1 NM_001034850.2(RETREG1):c.459-25093T>CSNV Benign 380792 rs332811 5:16508674-16508674 5:16508565-16508565
49 RETREG1 NM_001034850.2(RETREG1):c.816C>T (p.Asp272=)SNV Benign 352689 rs162848 5:16478200-16478200 5:16478091-16478091
50 RETREG1 NM_001034850.2(RETREG1):c.603T>C (p.Cys201=)SNV Benign 137274 rs16868675 5:16481185-16481185 5:16481076-16481076

Expression for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Search GEO for disease gene expression data for Neuropathy, Hereditary Sensory and Autonomic, Type Iib.

Pathways for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Pathways related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11 KIF1A HBD HBB
2 10.42 WNK1 STK39

GO Terms for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

Cellular components related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hemoglobin complex GO:0005833 8.96 HBD HBB
2 haptoglobin-hemoglobin complex GO:0031838 8.62 HBD HBB

Biological processes related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sensory perception of pain GO:0019233 9.46 SCN9A RETREG1
2 hydrogen peroxide catabolic process GO:0042744 9.43 HBD HBB
3 cellular response to chemokine GO:1990869 9.4 WNK1 STK39
4 oxygen transport GO:0015671 9.37 HBD HBB
5 positive regulation of T cell chemotaxis GO:0010820 9.32 WNK1 STK39
6 ion homeostasis GO:0050801 9.26 WNK1 STK39
7 positive regulation of ion transmembrane transporter activity GO:0032414 9.16 WNK1 STK39
8 negative regulation of pancreatic juice secretion GO:0090188 8.96 WNK1 STK39
9 signal transduction by trans-phosphorylation GO:0023016 8.62 WNK1 STK39

Molecular functions related to Neuropathy, Hereditary Sensory and Autonomic, Type Iib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.1 WNK1 STK39 SNRPA SCN9A RTN4 RETREG1
2 peroxidase activity GO:0004601 9.4 HBD HBB
3 oxygen binding GO:0019825 9.37 HBD HBB
4 oxygen carrier activity GO:0005344 9.26 HBD HBB
5 organic acid binding GO:0043177 9.16 HBD HBB
6 haptoglobin binding GO:0031720 8.96 HBD HBB
7 hemoglobin alpha binding GO:0031721 8.62 HBD HBB

Sources for Neuropathy, Hereditary Sensory and Autonomic, Type Iib

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57 OMIM via Orphanet
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68 SNOMED-CT via HPO
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