CDH17

Chr 8

cadherin 17

Also known as: CDH16, HPT-1, HPT1

NCBI Gene: 1015 ENSG00000079112 UniProt: Q12864

The protein is a calcium-dependent cell adhesion molecule that functions as an intestinal proton-dependent peptide transporter and contributes to morphological organization of the liver and intestine. Mutations cause congenital diarrheal disorders with early infantile onset, involving severe gastrointestinal dysfunction. The gene shows autosomal recessive inheritance and is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.96

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.74

OE 0.70 (0.51–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.35Z-score

OE missense 0.95 (0.88–1.03)

438 obs / 459.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.51–0.96)

0≤0.351.4

Missense OE?0.95 (0.88–1.03)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 27 / 38.7Missense obs/exp: 438 / 459.2Syn Z: -0.80

Background carrier burden — how many people carry a rare variant somewhere in CDH17?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

1,060 rare PASS variants

Rare truncating (LoF)

1 in 640

158 rare PASS variants

Rare synonymous (reference)

1 in 72

392 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDH17. 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 67	1 in 990
South Asian	~43k	1 in 37	1 in 190
Remaining (unassigned)	~30k	1 in 52	1 in 440
European (Finnish)	~27k	1 in 330	1 in 980
Admixed American	~22k	1 in 56	1 in 330
African / African American	~21k	1 in 55	1 in 590
East Asian	~20k	1 in 75	1 in 280
Ashkenazi Jewish	~13k	1 in 170	1 in 520
Middle Eastern	~2,884	1 in 72	≈ 1 in 960

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): 14 of 17 coding exons well covered in gnomAD exomes; exons 2, 11, 16 marginal. Genomes: 16 of 17 (exon 14 below).? see exons ↓