CEACAM16

Summary

CEACAM16 (CEA cell adhesion molecule 16, tectorial membrane component, HGNC:31948) is a protein-coding gene on chromosome 19q13.31-q13.32, encoding Cell adhesion molecule CEACAM16 (Q2WEN9). Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane.

The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss.

Source: NCBI Gene 388551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Strong, ClinGen) — +4 more curated relationships
• GWAS associations: 22
• Clinical variants (ClinVar): 306 total — 7 pathogenic, 5 likely-pathogenic (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 8 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 6
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.14 (unconstrained)
• MANE Select transcript: NM_001039213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31948
Approved symbol	CEACAM16
Name	CEA cell adhesion molecule 16, tectorial membrane component
Location	19q13.31-q13.32
Locus type	gene with protein product
Status	Approved
Aliases	DFNA4B
Ensembl gene	ENSG00000213892
Ensembl biotype	protein_coding
OMIM	614591
Entrez	388551

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000587331

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

ENST00000587331, ENST00000405314

RefSeq mRNA: 1 — MANE Select: NM_001039213 NM_001039213

CCDS: CCDS54278

Canonical transcript exons

ENST00000587331 — 7 exons

Exon	Start	End
ENSE00001526131	44705590	44705868
ENSE00001526132	44704018	44704296
ENSE00001526134	44703349	44703693
ENSE00002705110	44707861	44708187
ENSE00002876161	44701361	44701493
ENSE00002925332	44699151	44699260
ENSE00003841302	44710496	44710718

Expression profiles

Bgee: expression breadth broad, 26 present calls, max score 53.41.

Highest expression (Bgee): colonic epithelium, body of pancreas, mucosa of transverse colon, adrenal gland cortex, liver.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CEACAM16 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	5.4e-09	-0.40	19:44702322:T:C
Lung	eqtl	9.9e-05	-0.28	19:44685728:G:A
Adrenal Gland	eqtl	2.5e-04	+0.38	19:44705412:T:G
Pancreas	eqtl	6.6e-04	+0.35	19:44708135:T:C
Pituitary	eqtl	2.6e-03	-0.33	19:44702607:T:C
Colon Transverse	eqtl	3.8e-03	+0.18	19:44703262:A:G
Testis	eqtl	2.2e-02	-0.34	19:44639551:G:T
Muscle Skeletal	eqtl	4.2e-02	+0.16	19:44706173:C:G

Top tissues by expression

showing 100 of 110 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	53.41	gold quality
body of pancreas	UBERON:0001150	51.06	gold quality
mucosa of transverse colon	UBERON:0004991	50.35	gold quality
right adrenal gland cortex	UBERON:0035827	50.12	gold quality
left adrenal gland cortex	UBERON:0035825	48.96	gold quality
liver	UBERON:0002107	48.88	silver quality
left adrenal gland	UBERON:0001234	48.66	gold quality
right lobe of liver	UBERON:0001114	47.46	gold quality
right adrenal gland	UBERON:0001233	47.39	gold quality
adrenal gland	UBERON:0002369	46.12	gold quality
tonsil	UBERON:0002372	45.94	gold quality
pancreas	UBERON:0001264	44.49	gold quality
lower esophagus mucosa	UBERON:0035834	43.41	silver quality
bone marrow cell	CL:0002092	38.24	gold quality
muscle of leg	UBERON:0001383	37.93	gold quality
pituitary gland	UBERON:0000007	37.90	gold quality
transverse colon	UBERON:0001157	37.49	silver quality
gastrocnemius	UBERON:0001388	37.17	gold quality
sural nerve	UBERON:0015488	36.83	gold quality
rectum	UBERON:0001052	36.48	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
esophagus mucosa	UBERON:0002469	36.33	silver quality
apex of heart	UBERON:0002098	36.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.60	gold quality
granulocyte	CL:0000094	35.57	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
adenohypophysis	UBERON:0002196	35.24	silver quality
gall bladder	UBERON:0002110	34.46	silver quality
mucosa of stomach	UBERON:0001199	33.80	gold quality
bone marrow	UBERON:0002371	32.81	gold quality
esophagus	UBERON:0001043	32.12	silver quality
myometrium	UBERON:0001296	31.54	gold quality
right lung	UBERON:0002167	31.08	gold quality
urinary bladder	UBERON:0001255	31.00	gold quality
spleen	UBERON:0002106	30.56	gold quality
vagina	UBERON:0000996	30.17	gold quality
body of stomach	UBERON:0001161	30.14	gold quality
lymph node	UBERON:0000029	30.04	gold quality
kidney	UBERON:0002113	30.04	gold quality
blood	UBERON:0000178	29.96	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.87	gold quality
islet of Langerhans	UBERON:0000006	29.52	gold quality
vermiform appendix	UBERON:0001154	29.37	gold quality
cortex of kidney	UBERON:0001225	29.22	gold quality
saliva-secreting gland	UBERON:0001044	29.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	29.14	silver quality
subcutaneous adipose tissue	UBERON:0002190	28.96	gold quality
minor salivary gland	UBERON:0001830	28.87	gold quality
adipose tissue	UBERON:0001013	28.84	gold quality
omental fat pad	UBERON:0010414	28.83	gold quality
right atrium auricular region	UBERON:0006631	28.64	gold quality
adult mammalian kidney	UBERON:0000082	28.62	gold quality
multicellular organism	UBERON:0000468	28.27	gold quality
leukocyte	CL:0000738	28.17	gold quality
duodenum	UBERON:0002114	28.14	gold quality
right lobe of thyroid gland	UBERON:0001119	27.82	gold quality
monocyte	CL:0000576	27.65	gold quality
placenta	UBERON:0001987	27.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	27.31	gold quality
right coronary artery	UBERON:0001625	26.77	gold quality
endometrium	UBERON:0001295	26.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	25.99	gold quality
thyroid gland	UBERON:0002046	25.80	gold quality
left coronary artery	UBERON:0001626	25.58	gold quality
endocervix	UBERON:0000458	25.45	gold quality
calcaneal tendon	UBERON:0003701	25.26	gold quality
frontal cortex	UBERON:0001870	25.24	gold quality
prostate gland	UBERON:0002367	25.22	gold quality
left lobe of thyroid gland	UBERON:0001120	24.96	gold quality
ascending aorta	UBERON:0001496	24.96	gold quality
tibial nerve	UBERON:0001323	24.90	gold quality
substantia nigra	UBERON:0002038	24.83	silver quality
metanephros cortex	UBERON:0010533	24.77	gold quality
thoracic aorta	UBERON:0001515	24.69	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
ovary	UBERON:0000992	24.37	gold quality
body of uterus	UBERON:0009853	24.34	gold quality
adrenal tissue	UBERON:0018303	24.30	gold quality
tibial artery	UBERON:0007610	24.15	gold quality
popliteal artery	UBERON:0002250	24.11	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
left ovary	UBERON:0002119	23.80	gold quality
brain	UBERON:0000955	23.38	gold quality
hypothalamus	UBERON:0001898	23.34	gold quality
zone of skin	UBERON:0000014	22.84	gold quality
skin of leg	UBERON:0001511	22.79	gold quality
right ovary	UBERON:0002118	22.64	gold quality
skin of abdomen	UBERON:0001416	22.49	gold quality
cerebellum	UBERON:0002037	22.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	22.26	gold quality
cerebellar cortex	UBERON:0002129	22.25	gold quality
smooth muscle tissue	UBERON:0001135	22.15	gold quality
cerebellar hemisphere	UBERON:0002245	22.13	gold quality
anterior cingulate cortex	UBERON:0009835	21.09	gold quality
temporal lobe	UBERON:0001871	20.71	gold quality
Ammon’s horn	UBERON:0001954	20.71	gold quality
amygdala	UBERON:0001876	20.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	19.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

HPA expression

RNA tissue specificity: Tissue enhanced

36 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Superior colliculi	tissue	2.9
Cerebral cortex	tissue	2.5
Occipital cortex	tissue	2.5
Thalamus	tissue	2.4
Midbrain	tissue	2.3
Pons	tissue	2.2
Medulla oblongata	tissue	2.2
Somatosensory cortex	tissue	2.0
Pancreas	tissue	1.9
Spinal cord	tissue	1.9
Putamen	tissue	1.8
Retrosplenial and cingulate cortex	tissue	1.8
Temporal cortex	tissue	1.7
Hypothalamus	tissue	1.6
Cerebellum	tissue	1.6
Hippocampal formation	tissue	1.6
Entorhinal cortex	tissue	1.6
Ventral forebrain	tissue	1.6
Olfactory bulb	tissue	1.6
Retrosplenial cortex	tissue	1.6
Periaqueductal gray	tissue	1.5
Insular cortex	tissue	1.5
Motor cortex	tissue	1.4
Prefrontal cortex	tissue	1.3
Basal ganglia	tissue	1.3
Substantia nigra	tissue	1.3
Corpus callosum	tissue	1.3
Septum	tissue	1.3
Amygdala	tissue	1.2
Tonsil	tissue	0.5
Choroid plexus	tissue	0.4
Retina	tissue	0.2
Skeletal muscle	tissue	0.2
Locus coeruleus	tissue	0.2
Pituitary gland	tissue	0.1
Hippocampus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 66; highest nTPM — Ventral spinal cord (1.9), Dorsal hippocampus (1.4), White matter (1.3), Dorsal spinal cord (1.2), Ventral hippocampus (1.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CEACAM16 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-942-5P	99.41	68.40	1977

Functional genomics

gnomAD constraint: pLI 2.29e-09, LOEUF 1.14, missense Z 0.604 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000587331 — one region, missense o/e 0.89.

Literature-anchored findings (GeneRIF, showing 5)

• data identify CEACAM16 as an alpha-tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia and, when mutated, results in ADNSHL at the DFNA4 locus (PMID:21368133)
• CEACAM16 can probably form higher order structures with other tectorial membrane proteins such as alpha-tectorin and beta-tectorin and influences the physical properties of the tectorial membrane (PMID:22544735)
• Data indicate that a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16) was identified in autosomal dominant nonsyndromic hearing loss family. (PMID:25589040)
• Results confirm that CEACAM6 promoted cell proliferation mediated by cyclin D1/CDK4. (PMID:26497080)
• [Identification of a novel mutation of CEACAM16 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss]. (PMID:33040498)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ceacam16	ENSMUSG00000014686
rattus_norvegicus	Ceacam16	ENSRNOG00000031391

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM1 (ENSG00000079385), CEACAM6 (ENSG00000086548), CEACAM4 (ENSG00000105352), CEACAM5 (ENSG00000105388), PSG8 (ENSG00000124467), CEACAM8 (ENSG00000124469), HEPACAM (ENSG00000165478), PSG6 (ENSG00000170848), CEACAM3 (ENSG00000170956), PSG9 (ENSG00000183668), CEACAM19 (ENSG00000186567), HEPACAM2 (ENSG00000188175), PSG5 (ENSG00000204941), CEACAM18 (ENSG00000213822), VSTM5 (ENSG00000214376), PSG3 (ENSG00000221826), PSG7 (ENSG00000221878), PSG1 (ENSG00000231924), PSG2 (ENSG00000242221), PSG11 (ENSG00000243130), PSG4 (ENSG00000243137), CEACAM20 (ENSG00000273777)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685615) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased or absent threshold for auditory brainstem response	2
decreased circulating free fatty acids level	1
nonsyndromic hearing loss	1
increased circulating sodium level	1
abnormal otoacoustic response	1
sclerocornea	1
absent Hensen stripe	1
abnormal tectorial membrane striated-sheet matrix morphology	1
decreased distortion product otoacoustic emission threshold	1
decreased distortion product otoacoustic emission amplitude	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CEACAM16-AS1	ncRNA	107985305
CBLC	protein-coding	23624
BCL3	protein-coding	602
MIR8085	ncRNA	102465879
CEACAM19	protein-coding	56971
PVR	protein-coding	5817
MIR4531	ncRNA	100616355
BCAM	protein-coding	4059
IGSF23	protein-coding	147710

Protein

Protein identifiers

Cell adhesion molecule CEACAM16 — Q2WEN9 (reviewed: Q2WEN9)

Alternative names: Carcinoembryonic antigen-like 2, Carcinoembryonic antigen-related cell adhesion molecule 16

All UniProt accessions (1): Q2WEN9

UniProt curated annotations — full annotation on UniProt →

Function. Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane.

Subunit / interactions. Homooligomer; can for homodimers and homotetramers. Interacts with TECTA and TECTB.

Subcellular location. Secreted.

Disease relevance. Deafness, autosomal dominant, 4B (DFNA4B) [MIM:614614] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal recessive, 113 (DFNB113) [MIM:618410] A form of non-syndromic, sensorineural deafness characterized by postlingual progressive hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

RefSeq proteins (1): NP_001034302* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050831	CEA_cell_adhesion	Family

Pfam: PF07686, PF13895, PF13927

UniProt features (11 total): glycosylation site 3, sequence variant 2, domain 2, disulfide bond 2, signal peptide 1, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2WEN9-F1	90.50	0.80

Human Protein Atlas

Protein class: Predicted secreted proteins, Disease related genes, Human disease related genes, Ear disease

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2)

Type	Positions
Disulfide bond	153–201, 252–293

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	36, 216, 394

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 18 (showing top): GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, GOCC_STEREOCILIUM_BUNDLE, GOCC_CLUSTER_OF_ACTIN_BASED_CELL_PROJECTIONS, GOCC_ACTIN_BASED_CELL_PROJECTION, PEDRIOLI_MIR31_TARGETS_UP, GOCC_STEREOCILIUM_TIP, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, SUPT16H_TARGET_GENES, HP_VISUAL_IMPAIRMENT, HP_ABNORMAL_VESTIBULAR_FUNCTION, HP_JUVENILE_ONSET, HP_FUNCTIONAL_ABNORMALITY_OF_THE_INNER_EAR, HP_ABNORMALITY_OF_VISION

GO Biological Process (1): sensory perception of sound (GO:0007605)

GO Molecular Function (1): identical protein binding (GO:0042802)

GO Cellular Component (2): stereocilium tip (GO:0032426), extracellular region (GO:0005576)

GO top-level categories

4 GO namespaces:

Category	Terms
cellular anatomical structure	2
sensory perception of mechanical stimulus	1
protein binding	1
stereocilium	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
sensory perception of sound	BP	mutant phenotype
identical protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 466 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEACAM16	TECTB	Q96PL2	719
CEACAM16	TECTA	O75443	704
CEACAM16	OTOG	Q6ZRI0	606
CEACAM16	TPRN	Q4KMQ1	570
CEACAM16	STRC	Q7RTU9	570
CEACAM16	OTOGL	Q3ZCN5	570
CEACAM16	SMPX	Q9UHP9	558
CEACAM16	OTOA	Q7RTW8	539
CEACAM16	TSPEAR	Q8WU66	512
CEACAM16	LOXHD1	Q8IVV2	498
CEACAM16	CDH23	Q9H251	497
CEACAM16	LHFPL5	Q8TAF8	493
CEACAM16	SLC26A5	P58743	470
CEACAM16	TMC1	Q8TDI8	470
CEACAM16	MYO3A	Q8NEV4	464

IntAct

Human interaction partners of CEACAM16 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
SBNO1	association	0.350	1

BioGRID (13 interactions; top human partners by supporting records): CBL (Affinity Capture-MS), DST (Affinity Capture-MS), EEA1 (Affinity Capture-MS), GCA (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), MPP1 (Affinity Capture-MS), NSD1 (Affinity Capture-MS), ODF2 (Affinity Capture-MS), OXSR1 (Affinity Capture-MS), PSMG2 (Affinity Capture-MS), SBNO1 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), USO1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CEACAM16: 306 ClinVar records (12 pathogenic / likely pathogenic); 22 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

306 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	158
Likely benign	67
Benign	24

Top pathogenic / likely-pathogenic (12)

Showing all 12 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
626322	NM_001039213.4(CEACAM16):c.662-1G>C	Pathogenic	criteria provided, single submitter	2
2138305	NM_001039213.4(CEACAM16):c.859del (p.Gln287fs)	Pathogenic	criteria provided, single submitter	1
2856290	NM_001039213.4(CEACAM16):c.727_730dup (p.Phe244Ter)	Pathogenic	criteria provided, single submitter	1
3340146	NM_001039213.4(CEACAM16):c.436C>T (p.Arg146Ter)	Pathogenic	criteria provided, single submitter	1
3717767	NM_001039213.4(CEACAM16):c.325C>T (p.Gln109Ter)	Pathogenic	criteria provided, single submitter	1
626323	NM_001039213.4(CEACAM16):c.37G>T (p.Ala13Ser)	Likely pathogenic	criteria provided, single submitter	2
1180770	NM_001039213.4(CEACAM16):c.459C>A (p.Cys153Ter)	Likely pathogenic	criteria provided, single submitter	1
3765552	NM_001039213.4(CEACAM16):c.703dup (p.Arg235fs)	Likely pathogenic	criteria provided, single submitter	1
3779505	NM_001039213.4(CEACAM16):c.1203C>A (p.Tyr401Ter)	Likely pathogenic	criteria provided, single submitter	1
4077182	NM_001039213.4(CEACAM16):c.380A>G (p.His127Arg)	Likely pathogenic	criteria provided, single submitter	1
31238	NM_001039213.4(CEACAM16):c.418A>C (p.Thr140Pro)	Pathogenic	no assertion criteria provided	1
235136	NM_001039213.4(CEACAM16):c.505G>A (p.Gly169Arg)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CEACAM16’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 670):

Position(s)	Effect	Δscore	Sites
19:44705869–44705870	donor_loss	1.0000	5
19:44707859–44707860	acceptor_loss	1.0000	6
19:44704016–44704017	acceptor_loss	0.9900	6
19:44708150	donor_gain	0.9900
19:44708166	donor_gain	0.9900
19:44710363	donor_gain	0.9900
19:44710486	acceptor_gain	0.9900
19:44703347–44703348	acceptor_loss	0.9800	6
19:44703694–44703695	donor_loss	0.9800	6
19:44704297–44704298	donor_loss	0.9800	6

AlphaMissense

643 missense substitutions predicted likely pathogenic (of 2,707 scored), across 206 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N297	8	0.957	0.997
D397	8	0.927	0.981
C293	7	0.991	0.997
C252	7	0.988	0.996
C201	7	0.985	0.996
W264	7	0.979	0.998
W350	7	0.978	0.998
C153	7	0.975	0.992
W164	7	0.967	0.997
W53	7	0.963	0.994
C238	7	0.893	0.943
E144	7	0.889	0.964
N205	7	0.879	0.981
E380	7	0.842	0.926
F221	7	0.824	0.972
C257	7	0.813	0.862
F165	7	0.805	0.933
F383	7	0.786	0.917
E85	7	0.771	0.870
S212	6	0.963	0.993

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:614591 | disease phenotypes: MIM:128600, MIM:614614, MIM:220290, MIM:607197, MIM:618410

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
autosomal dominant nonsyndromic hearing loss 4B	Strong	Autosomal dominant
hearing loss, autosomal recessive 113	Strong	Autosomal recessive
nonsyndromic genetic hearing loss	Moderate	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Strong	AR
nonsyndromic genetic hearing loss	Moderate	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Monogenic hearing loss	green
Paediatric disorders	green

Mondo (6): ear malformation (MONDO:0007500), autosomal dominant nonsyndromic hearing loss 4B (MONDO:0013823), hearing loss, autosomal recessive (MONDO:0019588), hearing loss, autosomal recessive 113 (MONDO:0032732), nonsyndromic genetic hearing loss (MONDO:0019497), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (2): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636)

HPO phenotypes

6 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0001751	Abnormal vestibular function
HP:0003621	Juvenile onset

GWAS associations

22 associations:

Study	Trait	p-value
GCST010245_132	LDL cholesterol levels	0.000000e+00
GCST008079_67	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-273
GCST008079_2	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-213
GCST008078_144	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-177
GCST008086_55	LDL cholesterol levels in current drinkers	8e-89
GCST008078_109	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1e-83
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7e-74
GCST007827_6	Alzheimer’s disease or HDL levels (pleiotropy)	7e-54
GCST008077_5	LDL cholesterol levels	2e-49
GCST001947_2	Alzheimer’s disease (late onset)	5e-39
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3e-36
GCST008086_72	LDL cholesterol levels in current drinkers	8e-35
GCST008075_91	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-16
GCST008084_20	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6e-16
GCST010243_154	Apolipoprotein B levels	2e-15
GCST008077_33	LDL cholesterol levels	3e-14
GCST007827_17	Alzheimer’s disease or HDL levels (pleiotropy)	3e-12
GCST010243_71	Apolipoprotein B levels	1e-11
GCST009496_17	Alzheimer’s disease (onset between ages 58 and 79)	1e-10
GCST008084_235	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-10
GCST008075_189	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5e-9
GCST008085_55	HDL cholesterol levels in current drinkers	1e-7

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C564609	Deafness, Autosomal Recessive *(supp.)*
C580334	Nonsyndromic Deafness *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 301 trials:

NCT	Phase	Status	Title
NCT00205881	Phase 4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	Phase 4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	Phase 4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	Phase 4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	Phase 4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	Phase 3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	Phase 3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	Phase 3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	Phase 3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	Phase 2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	Phase 2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	Phase 2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	Phase 2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	Phase 2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	Phase 2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	Phase 2	UNKNOWN	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	Phase 2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	Phase 2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	Phase 2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	Phase 2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	Phase 1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	Phase 1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	Phase 1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	Phase 1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	Phase 1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	Phase 1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	Phase 1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	Phase 1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	Phase 1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT00486577	Phase 2/3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	Phase 2/3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	Phase 2/3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	Phase 2/3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	Phase 1/2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	Phase 1/2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	Phase 1/2	ACTIVE_NOT_RECRUITING	A Phase I/II Clinical Trial With SENS-501 in Children Suffering From Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	Phase 1/2	ACTIVE_NOT_RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	Phase 1/2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	Early Phase 1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss
NCT03300687	Early Phase 1	COMPLETED	First in Human Safety Study of FX-322 in Adults Undergoing Cochlear Implantation
NCT04777669	Early Phase 1	UNKNOWN	Removing Background Talker Noise for Cochlear Implant Users
NCT06025032	Early Phase 1	WITHDRAWN	a Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy(SOUND)
NCT00001668	Not specified	COMPLETED	Endolymphatic Sac Tumors in a Population of Patients With Von Hippel-Lindau Disease:The Natural History and Pathobiology, and a Prospective Non-Randomized Clinical Trial of Hearing Preservation Surgery in Patients With Early Stage Endolymphatic Sac Tumors
NCT00001782	Not specified	COMPLETED	Areas of Brain Responsible for Understanding American Sign Language
NCT00013468	Not specified	COMPLETED	Early Diagnosis of Steroid-Responsive & No-Responsive Hearing Loss
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00018486	Not specified	COMPLETED	Epidemiology of Hearing Loss in Diabetic and Non-Diabetic Veterans
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT00110604	Not specified	COMPLETED	The Effect of Folic Acid on Atherosclerosis, Cognitive Performance and Hearing
NCT00126113	Not specified	COMPLETED	The Performance-Perceptual Test as a Counseling Tool
NCT00260663	Not specified	COMPLETED	The Hearing Aid Effectiveness After Aural Rehabilitation (HEAR) Trial
NCT00371436	Not specified	COMPLETED	Progressive Intervention Program for Tinnitus Management
NCT00371449	Not specified	COMPLETED	Predicting Success With Hearing Aids
NCT00371839	Not specified	COMPLETED	Clinical Applications for Time-Compressed Speech Tests
NCT00400413	Not specified	COMPLETED	Neuroanatomy of Reading in Congenital Deafness.
NCT00438334	Not specified	COMPLETED	Real-World Benefit From Directional Hearing Aids
NCT00451503	Not specified	COMPLETED	Evaluation of Middle Ear Implantation
NCT00484224	Not specified	UNKNOWN	Audiological Disturbances in Vitiligo