CHRDL2

Chr 11

chordin like 2

Also known as: BNF1, CHL2

NCBI Gene: 25884 ENSG00000054938 UniProt: Q6WN34 OMIM: 613127

The protein encoded by this gene is a secreted member of the chordin family that inhibits bone morphogenetic protein (BMP) activity and negatively regulates cartilage formation from mesenchymal cells, with roles in myoblast and osteoblast differentiation. Mutations cause megalocornea-mental retardation syndrome, an X-linked recessive disorder characterized by enlarged corneas and intellectual disability. This gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the chordin family of proteins. Chordin family members are secreted proteins that share a cysteine-rich pro-collagen repeat domain and associate with members of the transforming growth factor beta superfamily. In vitro assays demonstrate a direct interaction between the encoded protein and human activin A. This gene is expressed in many tissues including osteoblasts, where it is differentially expressed during differentiation. In addition, its expression is upregulated in human osteoarthritic joint cartilage, suggesting a role in adult cartilage regeneration. [provided by RefSeq, Jan 2015]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.89

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 1.97

OE 0.56 (0.36–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.14Z-score

OE missense 0.80 (0.72–0.90)

215 obs / 267.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.36–0.89)

0≤0.351.4

Missense OE?0.80 (0.72–0.90)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 13 / 23.3Missense obs/exp: 215 / 267.6Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in CHRDL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

612 rare PASS variants

Rare truncating (LoF)

1 in 760

111 rare PASS variants

Rare synonymous (reference)

1 in 130

220 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHRDL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 1,800
South Asian	~43k	1 in 79	1 in 1,000
Remaining (unassigned)	~30k	1 in 110	1 in 820
European (Finnish)	~27k	1 in 530	1 in 2,600
Admixed American	~22k	1 in 93	1 in 250
African / African American	~21k	1 in 90	1 in 770
East Asian	~20k	1 in 110	1 in 770
Ashkenazi Jewish	~13k	1 in 420	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 86	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓