MCRS1

protein-coding

microspherule protein 1, the group of INO80 complex |NSL histone acetyltransferase complex

Gene summary

Enables RNA binding activity and telomerase inhibitor activity. Involved in several processes, including positive regulation of DNA-templated transcription; positive regulation of protein localization to nucleolus; and regulation of DNA metabolic process. Located in cytoplasm; nucleolus; and nucleoplasm. Part of Ino80 complex; MLL1 complex; and histone acetyltransferase complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006337.5

Inheritance

—

ClinVar variants

U:47B:1

Top phenotype

Multiple congenital anomalies/dysmorphic syndrome

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr12:49,556,544-49,568,145

External References & Databases

Ensembl (ENSG00000187778)

Transcript & Mutation Effects

hg38 • Region Span ~11.6 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 MCRS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

Multiple congenital anomalies/dysmorphic syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006337.5. 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 clinvar		2
missense			43 clinvar			43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	47	1	0	48

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006337.5	RefSeq	NP_006328.2	14	MANE Select
ENST00000343810.9	Ensembl	ENSP00000345358.4	14	MANE Select
NM_001012300.1	RefSeq	NP_001012300.1	14	Standard
NM_001278341.2	RefSeq	NP_001265270.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mcrs1	Danio rerio	Structure: retina Quality: apoptotic abnormal

Gene / Model

Organism

Observed Phenotype

mcrs1

Danio rerio

Structure: retina

Quality: apoptotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Herpes simplex infection - Homo sapiens (human)
DNA Repair
Post-translational protein modification
Metabolism of proteins
Chromatin modifying enzymes

Biological Process

DNA repair
DNA recombination
cellular protein modification process
protein deubiquitination
histone H4-K5 acetylation

Molecular Function

G-quadruplex RNA binding
protein binding
poly(U) RNA binding
poly(G) binding
histone acetyltransferase activity (H4-K5 specific)

Cellular Component

histone acetyltransferase complex
nucleus
nucleoplasm
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357123
Coding exons: 14
Length: 11610
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.20	187	293	0.639	0.0000181	3047
Missense (PolyPhen)		40	91.011	0.43951		941
Synonymous	-0.458	120	114	1.05	0.00000653	955
Loss of Function	3.69	7	28.1	0.249	0.00000154	297

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000072	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus (PubMed:11948183). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. May also be an inhibitor of TERT telomerase activity (PubMed:15044100). Binds to G-quadruplex structures in mRNA (PubMed:16571602). Binds to RNA homopolymer poly(G) and poly(U) (PubMed:16571602). {ECO:0000269|PubMed:11948183, ECO:0000269|PubMed:15044100, ECO:0000269|PubMed:16571602, ECO:0000269|PubMed:20018852}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.104
RVIS EVS: -0.47
RVIS percentile EVS: 23.25

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.948

Gene Damage Prediction

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