CRIM1

Chr 2

cysteine rich transmembrane BMP regulator 1

Also known as: CRIM-1, S52

This protein is a transmembrane receptor containing cysteine-rich domains that modulates bone morphogenetic protein (BMP) signaling and plays a role in CNS development, motor neuron survival, and angiogenesis. Mutations cause autosomal recessive disorders including arthrogryposis, renal dysfunction, and cholestasis syndrome, as well as autosomal dominant microcephaly, seizures, and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.24), indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
Clinical SummaryCRIM1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 157 VUS of 271 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 5.75
OE 0.12 (0.070.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.19Z-score
OE missense 0.98 (0.911.05)
587 obs / 600.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.070.24)
00.351.4
Missense OE0.98 (0.911.05)
00.61.4
Synonymous OE1.24
01.21.6
LoF obs/exp: 6 / 49.8Missense obs/exp: 587 / 600.4Syn Z: -2.84

ClinVar Variant Classifications

271 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic4
VUS157
Likely Benign22
Benign16
Conflicting1
15
Pathogenic
4
Likely Pathogenic
157
VUS
22
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
4
0
4
VUS
1
153
3
0
157
Likely Benign
0
11
4
7
22
Benign
0
4
3
9
16
Conflicting
1
Total11682916215

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

View in ClinVar →

Protein Context — Lollipop Plot

CRIM1 · 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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