CER1

Chr 9

cerberus 1, DAN family BMP antagonist

Also known as: DAND4

NCBI Gene: 9350 ENSG00000147869 UniProt: O95813 OMIM: 603777

The protein is a cytokine that inhibits bone morphogenetic protein (BMP) signaling and regulates Nodal signaling during embryonic development, particularly in anterior neural induction and somite formation. Mutations cause autosomal recessive neural tube defects including spina bifida and anencephaly. This gene is not highly constrained against loss-of-function variants, consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a cytokine member of the cysteine knot superfamily, characterized by nine conserved cysteines and a cysteine knot region. The cerberus-related cytokines, together with Dan and DRM/Gremlin, represent a group of bone morphogenetic protein (BMP) antagonists that can bind directly to BMPs and inhibit their activity. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.80

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.80LOEUF

pLI 0.000

Z-score -0.15

OE 1.06 (0.60–1.80)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.64Z-score

OE missense 1.38 (1.23–1.55)

203 obs / 147.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.06 (0.60–1.80)

0≤0.351.4

Missense OE?1.38 (1.23–1.55)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 7 / 6.6Missense obs/exp: 203 / 147.1Syn Z: -1.55

Background carrier burden — how many people carry a rare variant somewhere in CER1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

454 rare PASS variants

Rare truncating (LoF)

1 in 3,000

38 rare PASS variants

Rare synonymous (reference)

1 in 590

152 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CER1. 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 270	1 in 3,600
South Asian	~43k	1 in 110	1 in 5,400
Remaining (unassigned)	~30k	1 in 150	1 in 3,000
European (Finnish)	~27k	1 in 970	1 in 5,300
Admixed American	~22k	1 in 140	none seen
African / African American	~21k	1 in 110	1 in 3,800
East Asian	~20k	1 in 170	1 in 4,000
Ashkenazi Jewish	~13k	≈ 1 in 2,600	none seen
Middle Eastern	~2,884	1 in 160	none seen

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓