CMC4

protein-coding

C-X9-C motif containing 4

Gene summary

This gene was identified by involvement in some t(X;14) translocations associated with mature T-cell proliferations. This region has a complex gene structure, with a common promoter and 5' exon spliced to two different sets of 3' exons that encode two different proteins. This gene represents the downstream 8 kDa protein that localizes to mitochondria.[provided by RefSeq, Mar 2009]

Previous symbols:

MTCP1
MTCP1NB

MANE transcript

NM_001018024.3

Inheritance

—

ClinVar variants

U:22B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chrX:155,061,622-155,071,136

External References & Databases

Ensembl (ENSG00000182712)

NCBI Gene (100272147)

Transcript & Mutation Effects

hg38 • Region Span ~9.5 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 CMC4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 12

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001018024.3. 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			1 clinvar			1
missense			11 clinvar	1 clinvar		12
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	22	1	0	23

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001018024.3	RefSeq	NP_001018024.1	2	MANE Select
ENST00000369484.8	Ensembl	ENSP00000358496.3	2	MANE Select
ENST00000369479.1	Ensembl	ENSP00000358491.1	2	Standard
ENST00000369479.2	Ensembl	ENSP00000358491.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Mitochondrial protein import

Biological Process

cell population proliferation

Cellular Component

mitochondrion
mitochondrial intermembrane space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369484
Coding exons: 2
Length: 9741
Individuals with no LoFs: 124758
Homozygous LoFs: 1
Heterozygous LoFs: 2
Defined: 124761
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.170	24	26.5	0.907	0.00000221	433
Missense (PolyPhen)		7	8.2747	0.84595		146
Synonymous	-0.763	13	9.94	1.31	8.43e-7	114
Loss of Function	0.740	1	2.18	0.459	1.37e-7	44

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00023	0.00019	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Note=Overexpressed in T-cell leukemia bearing a t(X;14) translocation. {ECO:0000269|PubMed:8361760}.;

Intolerance Scores

RVIS EVS: 0.15
RVIS percentile EVS: 63.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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