XIRP2

protein-coding

xin actin binding repeat containing 2, the group of LIM domain containing

Gene summary

Enables actin filament binding activity. Predicted to be involved in actin filament organization and regulation of actin filament organization. Predicted to act upstream of or within cardiac muscle tissue morphogenesis; cell-cell junction organization; and ventricular septum development. Located in focal adhesion and stress fiber. Implicated in depressive disorder. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

CMYA3

MANE transcript

NM_152381.6

Inheritance

—

ClinVar variants

U:526B:158

Top phenotype

XIRP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr2:166,888,480-167,259,753

External References & Databases

Ensembl (ENSG00000163092)

Transcript & Mutation Effects

hg38 • Region Span ~371.3 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 XIRP2 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 577

not providedTotal: 92

XIRP2-related disorderTotal: 72

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Congenital heart defects, multiple types, 4Total: 1

BlepharophimosisTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152381.6. 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			3 clinvar	35 clinvar	14 clinvar	52
missense			522 clinvar	77 clinvar	29 clinvar	628
nonsense					1 clinvar	1
start loss				1 clinvar		1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)				1 clinvar		1
Total	0	0	526	114	44	684

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152381.6	RefSeq	NP_689594.4	9	MANE Select
ENST00000409195.6	Ensembl	ENSP00000386840.2	9	MANE Select
NM_001079810.4	RefSeq	NP_001073278.1	9	Standard
NM_001199143.2	RefSeq	NP_001186072.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ventricular septum development
biological_process
actin cytoskeleton organization
cell-cell junction organization
cardiac muscle tissue morphogenesis

Molecular Function

actin filament binding
alpha-actinin binding

Cellular Component

stress fiber
focal adhesion
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409195
Coding exons: 9
Length: 371267
Individuals with no LoFs: 123536
Homozygous LoFs: 2
Heterozygous LoFs: 1267
Defined: 124805
p: 0.00510

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.40	2073	1.79e+3	1.16	0.0000900	23549
Missense (PolyPhen)		631	558.54	1.1297		7866
Synonymous	-1.68	692	638	1.08	0.0000335	6619
Loss of Function	2.22	95	121	0.783	0.00000627	1669

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0049	0.0049	notable
Latino/Admixed American	0.0058	0.0058	notable
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0.012	0.012	notable
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.0052	0.0051	notable
South Asian	0.0046	0.0046	notable
Other	0.0036	0.0036	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protects actin filaments from depolymerization. {ECO:0000269|PubMed:15454575}.;

Recessive Scores

pRec: 0.0864

Intolerance Scores

LoFtool: 0.976
RVIS EVS: 1.46
RVIS percentile EVS: 95.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.615

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High