Autosomal recessive nonsyndromic hearing loss 26

Summary

Autosomal recessive nonsyndromic hearing loss 26 (MONDO:0011553) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 26
Mondo ID	MONDO:0011553
MeSH	C565329
OMIM	605428
DOID	DOID:0110484
UMLS	C1854275
MedGen	340185
GARD	0022599
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 26 · autosomal recessive nonsyndromic deafness 26 · autosomal recessive nonsyndromic deafness type 26 · deafness, autosomal recessive 26 · DFNB26

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 26

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
545492	NM_002039.4(GAB1):c.347G>A (p.Gly116Glu)	GAB1	Pathogenic	criteria provided, single submitter
3066331	NM_002039.4(GAB1):c.1460_1462del (p.Met487_Gln488delinsLys)	GAB1	Uncertain significance	criteria provided, single submitter
983425	NC_000004.12:g.143428960_143495936dup	GAB1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GAB1	Limited	Unknown	autosomal recessive nonsyndromic hearing loss 26
PIGU	Limited	Unknown	autosomal recessive nonsyndromic hearing loss 26	6

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PIGU	HGNC:15791	ENSG00000101464	Q9H490	GPI-anchor transamidase component PIGU	gencc,clinvar
GAB1	HGNC:4066	ENSG00000109458	Q13480	GRB2-associated-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PIGU	GPI-anchor transamidase component PIGU	Component of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis.
GAB1	GRB2-associated-binding protein 1	Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PIGU	Other/Unknown	no		PIG-U
GAB1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, Gab1-4-like

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
mucosa of transverse colon	1
ventricular zone	1
colonic epithelium	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PIGU	240	ubiquitous	marker	mucosa of transverse colon, ganglionic eminence, ventricular zone
GAB1	278	ubiquitous	marker	secondary oocyte, oocyte, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GAB1	1,982
PIGU	720

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GAB1	Q13480	5
PIGU	Q9H490	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MET activates PTPN11	1	1142.0×	0.006	GAB1
MET activates PI3K/AKT signaling	1	951.7×	0.006	GAB1
Activated NTRK2 signals through PI3K	1	815.7×	0.006	GAB1
Attachment of GPI anchor to uPAR	1	634.4×	0.006	PIGU
MET receptor recycling	1	571.0×	0.006	GAB1
MET activates RAP1 and RAC1	1	519.1×	0.006	GAB1
Signaling by FGFR4 in disease	1	475.8×	0.006	GAB1
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	475.8×	0.006	GAB1
Constitutive Signaling by EGFRvIII	1	356.9×	0.006	GAB1
PI3K events in ERBB2 signaling	1	335.9×	0.006	GAB1
Signaling by ERBB2 ECD mutants	1	335.9×	0.006	GAB1
GAB1 signalosome	1	317.2×	0.006	GAB1
PI-3K cascade:FGFR3	1	317.2×	0.006	GAB1
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	285.5×	0.006	GAB1
PI-3K cascade:FGFR4	1	285.5×	0.006	GAB1
PI-3K cascade:FGFR1	1	259.6×	0.006	GAB1
PI-3K cascade:FGFR2	1	248.3×	0.006	GAB1
Signaling by FGFR3 in disease	1	248.3×	0.006	GAB1
Signaling by ERBB2 KD Mutants	1	211.5×	0.006	GAB1
Signaling by FGFR1 in disease	1	146.4×	0.009	GAB1
PI3K Cascade	1	135.9×	0.009	GAB1
Signaling by FGFR2 in disease	1	132.8×	0.009	GAB1
RET signaling	1	129.8×	0.009	GAB1
Constitutive Signaling by Aberrant PI3K in Cancer	1	63.4×	0.017	GAB1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.021	GAB1
PIP3 activates AKT signaling	1	33.4×	0.030	GAB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
GPI anchored protein biosynthesis	1	1404.3×	0.006	PIGU
attachment of GPI anchor to protein	1	1053.2×	0.006	PIGU
endothelial cell chemotaxis	1	842.6×	0.006	GAB1
regulation of receptor signaling pathway via JAK-STAT	1	702.2×	0.006	PIGU
vascular endothelial growth factor signaling pathway	1	526.6×	0.006	GAB1
GPI anchor biosynthetic process	1	247.8×	0.011	PIGU
positive regulation of blood vessel endothelial cell migration	1	195.9×	0.011	GAB1
vasodilation	1	183.2×	0.011	GAB1
epidermal growth factor receptor signaling pathway	1	123.9×	0.013	GAB1
insulin receptor signaling pathway	1	110.9×	0.013	GAB1
cellular response to mechanical stimulus	1	108.0×	0.013	GAB1
positive regulation of angiogenesis	1	57.7×	0.023	GAB1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	39.2×	0.031	GAB1
angiogenesis	1	31.2×	0.036	GAB1
intracellular signal transduction	1	19.1×	0.055	GAB1
signal transduction	1	8.0×	0.121	GAB1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIGU	0	0
GAB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GAB1	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PIGU, GAB1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PIGU	0	—
GAB1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.