NEO1

Chr 15

neogenin 1

Also known as: IGDCC2, NGN, NTN1R2

NCBI Gene: 4756 ENSG00000067141 UniProt: Q92859

This gene encodes a cell surface protein that is a member of the immunoglobulin superfamily. The encoded protein consists of four N-terminal immunoglobulin-like domains, six fibronectin type III domains, a transmembrane domain and a C-terminal internal domain that shares homology with the tumor suppressor candidate gene DCC. This protein may be involved in cell growth and differentiation and in cell-cell adhesion. Defects in this gene are associated with cell proliferation in certain cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

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GeneReview available — NEO1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.244

Z-score 6.11

OE 0.23 (0.16–0.35)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.63Z-score

OE missense 0.84 (0.79–0.89)

673 obs / 803.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.16–0.35)

0≤0.351.4

Missense OE?0.84 (0.79–0.89)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 17 / 73.5Missense obs/exp: 673 / 803.2Syn Z: 0.85

Background carrier burden — how many people carry a rare variant somewhere in NEO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,765 rare PASS variants

Rare truncating (LoF)

1 in 3,200

111 rare PASS variants

Rare synonymous (reference)

1 in 65

697 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEO1. 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 47	1 in 4,300
South Asian	~43k	1 in 31	1 in 2,100
Remaining (unassigned)	~30k	1 in 34	1 in 2,900
European (Finnish)	~27k	1 in 98	1 in 1,700
Admixed American	~22k	1 in 33	1 in 1,500
African / African American	~21k	1 in 35	1 in 1,800
East Asian	~20k	1 in 43	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 41	≈ 1 in 2,900

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): 27 of 29 coding exons well covered in gnomAD exomes; exons 1, 12 marginal. Genomes: 27 of 29 (exons 1, 5 below).? see exons ↓