MCTS1

protein-coding

MCTS1 re-initiation and release factor

Gene summary

Enables RNA cap binding activity; ribosomal small subunit binding activity; and translation initiation factor activity. Involved in IRES-dependent viral translational initiation; cytoplasmic translational initiation; and ribosome disassembly. Located in cytosol. Is active in cytoplasm. Implicated in immunodeficiency 118. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014060.3

Inheritance

ClinVar variants

P:3U:45B:2

Top phenotype

Immunodeficiency 118, mycobacteriosis

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:120,594,010-120,621,159

External References & Databases

Ensembl (ENSG00000232119)

Transcript & Mutation Effects

hg38 • Region Span ~27.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 118STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0958030

Submitter: PanelApp Australia

immunodeficiency 118MODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0958030

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Immunodeficiency 118, mycobacteriosisXL

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described as being at increased risk of disseminated mycobacterial infections including after BCG vaccination, and awareness may allow preventative measures and early and aggressive treatment of infections

Refs: 37875108

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCTS1 variants in ClinVar

3 Conditions Cataloged

Inborn genetic diseasesTotal: 5

Immunodeficiency 118Total: 3

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014060.3. 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			4 clinvar	1 clinvar		5
missense			25 clinvar		1 clinvar	26
nonsense			2 clinvar			2
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)	1 clinvar		14 clinvar			15
Total	3	0	45	1	1	50

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014060.3	RefSeq	NP_054779.1	6	MANE Select
ENST00000371317.10	Ensembl	ENSP00000360367.5	6	MANE Select
NM_001137554.2	RefSeq	NP_001131026.1	6	Standard
ENST00000371315.3	Ensembl	ENSP00000360365.3	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

formation of translation preinitiation complex
translation reinitiation
cellular response to DNA damage stimulus
cell cycle
positive regulation of cell population proliferation

Molecular Function

translation initiation factor activity
protein binding

Cellular Component

cytosol
plasma membrane
cytosolic small ribosomal subunit

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371315
Coding exons: 6
Length: 27065
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	15	59.4	0.253	0.00000381	1202
Missense (PolyPhen)		0	14.373	0		309
Synonymous	0.860	14	18.7	0.747	0.00000119	318
Loss of Function	2.41	0	6.78	0.00	4.99e-7	135

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
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

Function: FUNCTION: Anti-oncogene that plays a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constitutively expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role as translation enhancer; recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; up- regulates protein levels of BCL2L2, TFDP1, MRE11, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiples chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3. Involved in translation initiation; promotes aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. {ECO:0000269|PubMed:10440924, ECO:0000269|PubMed:11709712, ECO:0000269|PubMed:12637315, ECO:0000269|PubMed:15897892, ECO:0000269|PubMed:16322206, ECO:0000269|PubMed:16982740, ECO:0000269|PubMed:17016429, ECO:0000269|PubMed:17416211, ECO:0000269|PubMed:20713520, ECO:0000269|PubMed:9766643}.;

Recessive Scores

pRec: 0.198

Intolerance Scores

RVIS EVS: 0.32
RVIS percentile EVS: 72.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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