CMTM6

protein-coding

CKLF like MARVEL transmembrane domain containing 6, the group of CKLF like MARVEL transmembrane domain containing

Gene summary

This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene is widely expressed in many tissues, but the exact function of the encoded protein is unknown. [provided by RefSeq, Jul 2008]

Previous symbols:

CKLFSF6

MANE transcript

NM_017801.3

Inheritance

—

ClinVar variants

U:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr3:32,481,312-32,502,852

External References & Databases

Ensembl (ENSG00000091317)

Transcript & Mutation Effects

hg38 • Region Span ~21.5 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 CMTM6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017801.3. 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						0
missense			18 clinvar			18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	18	0	0	18

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017801.3	RefSeq	NP_060271.1	4	MANE Select
ENST00000205636.4	Ensembl	ENSP00000205636.3	4	MANE Select
ENST00000855852.1	Ensembl	ENSP00000525911.1	4	Standard
ENST00000855852.2	Ensembl	ENSP00000525911.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

protein transport
regulation of protein stability
endocytic recycling
neutrophil degranulation

Molecular Function

protein binding

Cellular Component

plasma membrane
membrane
integral component of membrane
early endosome membrane
azurophil granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000205636
Coding exons: 4
Length: 22097
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125706
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.505	74	87.3	0.848	0.00000389	1156
Missense (PolyPhen)		15	32.014	0.46855		465
Synonymous	-0.294	35	32.9	1.07	0.00000142	369
Loss of Function	1.75	1	5.38	0.186	2.23e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000033	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Associates with both constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where it protects PD-L1/CD274 from being targeted for lysosomal degradation, likely by preventing its STUB1-mediated ubiquitination. May stabilize PD-L1/CD274 expression on antigen presenting cells and potentiates inhibitory signaling by PDCD1/CD279, its receptor on T-cells, ultimately triggering T-cell anergy. {ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.;

Recessive Scores

pRec: 0.0943

Intolerance Scores

LoFtool: 0.347
RVIS EVS: 0.08
RVIS percentile EVS: 59.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium