CHRD

Chr 3

chordin

NCBI Gene: 8646 ENSG00000090539 UniProt: Q9H2X0 OMIM: 603475

This gene encodes a secreted protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta-like bone morphogenetic proteins and sequestering them in latent complexes. The encoded protein may also have roles in organogenesis and during adulthood. It has been suggested that this gene could be a candidate gene for Cornelia de Lange syndrome. Reduced expression of this gene results in enhanced bone regeneration. Alternative splicing results in multiple transcript variants. Other alternative splice variants have been described but their full length sequence has not been determined. [provided by RefSeq, Jan 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.52

Clinical Summary— CHRD

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Gene-Disease Validity (ClinGen)

congenital heart disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

154 VUS of 196 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.000

Z-score 4.26

OE 0.34 (0.23–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.46Z-score

OE missense 0.83 (0.77–0.89)

462 obs / 559.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.23–0.52)

0≤0.351.4

Missense OE?0.83 (0.77–0.89)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 17 / 49.3Missense obs/exp: 462 / 559.3Syn Z: -0.33

This gene — mechanism propensity

0.6357th %ile

GOF

0.5661th %ile

LOF

0.3744th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

196 submitted variants in ClinVar

ClinVar

Classification Summary

VUS154

Likely Benign11

Benign5

154

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	153	0	0	154
Likely Benign	0	9	0	2	11
Benign	0	1	1	3	5
Total	1	163	1	5	170

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

View in ClinVar →

42 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap CHRD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →