CEMIP

Chr 15

cell migration inducing hyaluronidase 1

Also known as: CCSP1, CEMIP1, HYBID, KIAA1199, TMEM2L

NCBI Gene: 57214 ENSG00000103888 UniProt: Q8WUJ3 OMIM: 608366

The protein mediates depolymerization of hyaluronic acid through clathrin-coated pit endocytosis and is involved in hyaluronan catabolism in skin and synovium. Mutations cause autosomal recessive nonsyndromic hearing loss (DFNB84). The gene shows high constraint against loss-of-function variants, suggesting complete loss of protein function is not well tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including clathrin heavy chain binding activity; hyaluronic acid binding activity; and hyalurononglucosaminidase activity. Involved in several processes, including hyaluronan catabolic process; positive regulation of protein phosphorylation; and positive regulation of protein targeting to membrane. Located in several cellular components, including clathrin-coated endocytic vesicle; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.73

Clinical Summary— CEMIP

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

176 VUS of 263 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 3.41

OE 0.56 (0.43–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.66Z-score

OE missense 0.83 (0.78–0.89)

648 obs / 778.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.43–0.73)

0≤0.351.4

Missense OE?0.83 (0.78–0.89)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 38 / 68.4Missense obs/exp: 648 / 778.4Syn Z: -0.76

ClinVar Variant Classifications

263 submitted variants in ClinVar

ClinVar

Classification Summary

VUS176

Likely Benign28

Benign58

Conflicting1

176

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	176	0	0	176
Likely Benign	0	13	2	13	28
Benign	0	4	41	13	58
Conflicting	—				1
Total	0	193	43	26	263

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap CEMIP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →