autosomal dominant nonsyndromic hearing loss 4B

Summary

autosomal dominant nonsyndromic hearing loss 4B (MONDO:0013823) is a disease caused by CEACAM16 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CEACAM16 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 4B
Mondo ID	MONDO:0013823
OMIM	614614
DOID	DOID:0110574
UMLS	C3281297
MedGen	482927
GARD	0018136
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 4B · autosomal dominant nonsyndromic deafness 4B · autosomal dominant nonsyndromic deafness caused by mutation in CEACAM16 · autosomal dominant nonsyndromic deafness type 4B · CEACAM16 autosomal dominant nonsyndromic deafness · deafness, autosomal dominant 4B · deafness, autosomal dominant 4b · deafness, autosomal dominant type 4B · DFNA4B

Data availability: 15 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 dominant disease › autosomal dominant nonsyndromic hearing loss › autosomal dominant nonsyndromic hearing loss 4B

Related subtypes (75): autosomal dominant nonsyndromic hearing loss 1, autosomal dominant nonsyndromic hearing loss 2A, autosomal dominant nonsyndromic hearing loss 4A, autosomal dominant nonsyndromic hearing loss 6, autosomal dominant nonsyndromic hearing loss 5, autosomal dominant nonsyndromic hearing loss 10, autosomal dominant nonsyndromic hearing loss 11, autosomal dominant nonsyndromic hearing loss 9, autosomal dominant nonsyndromic hearing loss 7, autosomal dominant nonsyndromic hearing loss 12, autosomal dominant nonsyndromic hearing loss 3A, autosomal dominant nonsyndromic hearing loss 13, autosomal dominant nonsyndromic hearing loss 15, autosomal dominant nonsyndromic hearing loss 17, autosomal dominant nonsyndromic hearing loss 16, autosomal dominant nonsyndromic hearing loss 20, autosomal dominant nonsyndromic hearing loss 23, autosomal dominant nonsyndromic hearing loss 25, autosomal dominant nonsyndromic hearing loss 18, autosomal dominant nonsyndromic hearing loss 24, autosomal dominant nonsyndromic hearing loss 22, autosomal dominant nonsyndromic hearing loss 30, autosomal dominant nonsyndromic hearing loss 36, autosomal dominant nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 44, autosomal dominant nonsyndromic hearing loss 48, autosomal dominant nonsyndromic hearing loss 41, autosomal dominant nonsyndromic hearing loss 49, autosomal dominant nonsyndromic hearing loss 43, autosomal dominant nonsyndromic hearing loss 28, autosomal dominant nonsyndromic hearing loss 31, autosomal dominant nonsyndromic hearing loss 47, autosomal dominant auditory neuropathy 1, autosomal dominant nonsyndromic hearing loss 53, autosomal dominant nonsyndromic hearing loss 27, autosomal dominant nonsyndromic hearing loss 59, autosomal dominant nonsyndromic hearing loss 3B, autosomal dominant nonsyndromic hearing loss 2B, autosomal dominant nonsyndromic hearing loss 50, autosomal dominant nonsyndromic hearing loss 51, autosomal dominant nonsyndromic hearing loss 64, autosomal dominant nonsyndromic hearing loss 33, autosomal dominant nonsyndromic hearing loss 56, autosomal dominant nonsyndromic hearing loss 54, autosomal dominant nonsyndromic hearing loss 58, autosomal dominant nonsyndromic hearing loss 65, autosomal dominant nonsyndromic hearing loss 67, autosomal dominant nonsyndromic hearing loss 40, autosomal dominant nonsyndromic hearing loss 69, autosomal dominant nonsyndromic hearing loss 68, autosomal dominant nonsyndromic hearing loss 70, autosomal dominant nonsyndromic hearing loss 66, hearing loss, autosomal dominant 74, hearing loss, autosomal dominant 77, hearing loss, autosomal dominant 81, hearing loss, autosomal dominant 82, hearing loss, autosomal dominant 83, hearing loss, autosomal dominant 84, hearing loss, autosomal dominant 80, hearing loss, autosomal dominant 37, hearing loss, autosomal dominant 75, hearing loss, autosomal dominant 76, hearing loss, autosomal dominant 71, hearing loss, autosomal dominant 72, hearing loss, autosomal dominant 73, hearing loss, autosomal dominant 34, with or without inflammation, hearing loss, autosomal dominant 78, hearing loss, autosomal dominant 79, hearing loss, autosomal dominant 85, hearing loss, autosomal dominant 86, hearing loss, autosomal dominant 87, hearing loss, autosomal dominant 88, hearing loss, autosomal dominant 89, hearing loss, autosomal dominant 90, autosomal dominant nonsyndromic hearing loss 91

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

15 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 conflicting classifications of pathogenicity, 3 pathogenic, 2 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1185559	NM_001039213.4(CEACAM16):c.763A>G (p.Arg255Gly)	CEACAM16	Pathogenic	no assertion criteria provided
235136	NM_001039213.4(CEACAM16):c.505G>A (p.Gly169Arg)	CEACAM16	Pathogenic	no assertion criteria provided
31238	NM_001039213.4(CEACAM16):c.418A>C (p.Thr140Pro)	CEACAM16	Pathogenic	no assertion criteria provided
3765552	NM_001039213.4(CEACAM16):c.703dup (p.Arg235fs)	CEACAM16	Likely pathogenic	criteria provided, single submitter
3779505	NM_001039213.4(CEACAM16):c.1203C>A (p.Tyr401Ter)	CEACAM16	Likely pathogenic	criteria provided, single submitter
1341605	NM_001039213.4(CEACAM16):c.164C>T (p.Ala55Val)	CEACAM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1484989	NM_001039213.4(CEACAM16):c.1097C>T (p.Pro366Leu)	CEACAM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
667086	NM_001039213.4(CEACAM16):c.565C>T (p.His189Tyr)	CEACAM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
667087	NM_001039213.4(CEACAM16):c.520G>A (p.Ala174Thr)	CEACAM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034399	NM_001039213.4(CEACAM16):c.245C>T (p.Thr82Met)	CEACAM16	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034400	NM_001039213.4(CEACAM16):c.-8G>A	CEACAM16	Uncertain significance	criteria provided, single submitter
1065067	NM_001039213.4(CEACAM16):c.1135C>T (p.Arg379Trp)	CEACAM16	Uncertain significance	criteria provided, multiple submitters, no conflicts
283090	NM_001039213.4(CEACAM16):c.1191C>A (p.Asp397Glu)	CEACAM16	Uncertain significance	criteria provided, multiple submitters, no conflicts
504817	NM_001039213.4(CEACAM16):c.234C>T (p.Gly78=)	CEACAM16	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
514246	NM_001039213.4(CEACAM16):c.95_96delinsTT (p.Ser32Ile)	CEACAM16	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
CEACAM16	Strong	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 4B	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEACAM16	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
CEACAM16	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CEACAM16	HGNC:31948	ENSG00000213892	Q2WEN9	Cell adhesion molecule CEACAM16	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEACAM16	Cell adhesion molecule CEACAM16	Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEACAM16	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
colonic epithelium	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEACAM16	26		yes	colonic epithelium, body of pancreas, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEACAM16	1,023

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEACAM16	Q2WEN9	90.50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sensory perception of sound	1	100.9×	0.010	CEACAM16

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CEACAM16	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	CEACAM16
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEACAM16	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.