CEMIP
protein-codingcell migration inducing hyaluronidase 1, the group of Hyaluronidases
Gene summary
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]
- KIAA1199
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~172.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019497
Submitter: ClinGen
KIAA1199 (CEMIP) was first reported in relation to autosomal recessive nonsyndromic hearing loss in 2003 (Abe et al., PMID: 14577002). At least 1 synonymous and 3 missense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Two probands were noted to have affected siblings, however these siblings were not sequenced or well phenotyped. One individual was reported as compound heterozygous, and shown to have inherited one variant from each unaffected parent. The other 3 cases are reported as heterozygous, with no inheritance information or parental sequencing. This gene-disease association is supported by expression studies that show the gene to be expressed in the cochlea of the mouse, rat and marmoset. In summary, there is no convincing genetic evidence supporting the association between KIAA1199 and nonsyndromic hearing loss, so this association is disputed. More evidence is needed to either support or refute the role KIAA1199 plays in this disease. This classification was approved by the ClinGen Hearing Loss Working Group on 7/17/2018.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CEMIP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001293298.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 10 | 24 | |||
| missense | 178 | 14 | 3 | 195 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 178 | 28 | 13 | 219 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001280227.1 | 28 | MANE Select | |
| Ensembl | ENSP00000378177.3 | 28 | MANE Select | |
| RefSeq | NP_001280233.1 | 28 | Standard | |
| RefSeq | NP_061159.1 | 28 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hyaluronan biosynthesis and export
- Hyaluronan metabolism
- Metabolism of carbohydrates
- Glycosaminoglycan metabolism
- Metabolism
Biological Process
- sensory perception of sound
- positive regulation of peptidyl-threonine phosphorylation
- hyaluronan biosynthetic process
- hyaluronan catabolic process
- positive regulation of cell migration
Molecular Function
- hyalurononglucosaminidase activity
- protein binding
- hyaluronic acid binding
- clathrin heavy chain binding
- ER retention sequence binding
Cellular Component
- extracellular region
- nucleus
- cytoplasm
- endoplasmic reticulum
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394685
- Coding exons
- 28
- Length
- 172434
- Individuals with no LoFs
- 125654
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 94
- Defined
- 125748
- p
- 0.000374
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 648 | 778 | 0.833 | 0.0000493 | 9033 |
| Missense (PolyPhen) | 240 | 334.64 | 0.71718 | 3779 | ||
| Synonymous | -0.762 | 328 | 311 | 1.05 | 0.0000224 | 2560 |
| Loss of Function | 3.41 | 38 | 68.4 | 0.556 | 0.00000371 | 785 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.0013 | 0.0013 | notable |
| East Asian | 0.00098 | 0.00098 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial- mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC- dependent manner. May be involved in hearing. {ECO:0000269|PubMed:23509262, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:24269685}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- RVIS EVS
- -1.05
- RVIS percentile EVS
- 7.63
Essentials
- Essential (gene trap)
- N