CEMIP2

protein-coding

cell migration inducing hyaluronidase 2, the group of Hyaluronidases

Gene summary

This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]

Previous symbols:

TMEM2

MANE transcript

NM_013390.3

Inheritance

—

ClinVar variants

P:2U:222B:14

Top phenotype

Congenital heart disease

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr9:71,683,366-71,816,690

External References & Databases

Ensembl (ENSG00000135048)

Transcript & Mutation Effects

hg38 • Region Span ~133.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEMIP2 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 215

not providedTotal: 6

Congenital heart diseaseTotal: 5

Retinal dystrophyTotal: 2

Inguinal herniaTotal: 2

Abnormal sternum morphologyTotal: 2

MyopiaTotal: 2

Joint laxityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013390.3. 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			7 clinvar	4 clinvar		11
missense	1 clinvar		210 clinvar	10 clinvar		221
nonsense	1 clinvar					1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	2	0	222	14	0	238

Highest pathogenic variant AF is 0.0000068458735

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013390.3	RefSeq	NP_037522.1	23	MANE Select
ENST00000377044.9	Ensembl	ENSP00000366243.4	23	MANE Select
NM_001135820.2	RefSeq	NP_001129292.1	22	Standard
NM_001349784.2	RefSeq	NP_001336713.1	16	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cemip2	Danio rerio	Structure: fast muscle cell Quality: detached from abnormal

Gene / Model

Organism

Observed Phenotype

cemip2

Danio rerio

Structure: fast muscle cell

Quality: detached from

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

angiogenesis
hyaluronan catabolic process
regulation of sprouting angiogenesis

Molecular Function

hyalurononglucosaminidase activity
calcium ion binding
cadherin binding

Cellular Component

integral component of plasma membrane
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377044
Coding exons: 23
Length: 133325
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 125748
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.918	698	770	0.907	0.0000417	9099
Missense (PolyPhen)		107	159.5	0.67085		1841
Synonymous	0.467	274	284	0.965	0.0000159	2668
Loss of Function	3.94	32	66.7	0.479	0.00000361	782

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00049	0.00048	rare
South Asian	0.000098	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell surface hyaluronidase that mediates the initial cleavage of extracellular high-molecular-weight hyaluronan into intermediate-size hyaluronan of approximately 5 kDa fragments (PubMed:28246172). Acts as a regulator of angiogenesis and heart morphogenesis by mediating degradation of extracellular hyaluronan, thereby regulating VEGF signaling (By similarity). Is very specific to hyaluronan; not able to cleave chondroitin sulfate or dermatan sulfate (PubMed:28246172). {ECO:0000250|UniProtKB:A3KPQ7, ECO:0000269|PubMed:28246172}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

RVIS EVS: -0.47
RVIS percentile EVS: 22.84

Essentials

Essential (gene trap): N