XIRP1

Chr 3

xin actin binding repeat containing 1

Also known as: CMYA1, Xin

Xin actin-binding repeat-containing protein 1 protects actin filaments from depolymerization and is required for cardiac intercalated disk structure, heart rhythm maintenance, and skeletal muscle development. Mutations cause dilated cardiomyopathy with conduction defects and myopathy with autosomal recessive inheritance. This gene is not highly constrained against loss-of-function variation, affecting primarily cardiac and skeletal muscle systems.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.17
Clinical SummaryXIRP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 166 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 0.55
OE 0.92 (0.731.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.35Z-score
OE missense 1.03 (0.981.08)
1080 obs / 1048.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.92 (0.731.17)
00.351.4
Missense OE1.03 (0.981.08)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 48 / 52.3Missense obs/exp: 1080 / 1048.3Syn Z: -1.43
DN
0.5575th %ile
GOF
0.6443th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic3
VUS166
Likely Benign7
Benign17
3
Pathogenic
166
VUS
7
Likely Benign
17
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
1
165
0
0
166
Likely Benign
0
6
0
1
7
Benign
0
12
0
5
17
Total118336193

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XIRP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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