CHORDC1

Chr 11

cysteine and histidine rich domain containing 1

Also known as: CHP1

The CHORDC1 protein functions as a co-chaperone for HSP90 and regulates centrosome duplication by inhibiting ROCK2 kinase activity, while also ensuring proper localization of EGFR to the plasma membrane. Mutations cause autosomal recessive scoliosis with intellectual disability, typically presenting in childhood with progressive spinal curvature and developmental delays. The gene is highly constrained against loss-of-function variants (pLI = 0.90, LOEUF = 0.38), indicating intolerance to haploinsufficiency in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.38
Clinical SummaryCHORDC1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 43 VUS of 76 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.902
Z-score 3.61
OE 0.14 (0.070.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.74Z-score
OE missense 0.84 (0.730.96)
136 obs / 162.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.070.38)
00.351.4
Missense OE0.84 (0.730.96)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 3 / 20.7Missense obs/exp: 136 / 162.7Syn Z: -1.20

ClinVar Variant Classifications

76 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS43
Likely Benign1
Benign1
16
Pathogenic
1
Likely Pathogenic
43
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
35
8
0
43
Likely Benign
0
0
1
0
1
Benign
0
0
1
0
1
Total03527062

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

View in ClinVar →

Protein Context — Lollipop Plot

CHORDC1 · 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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