NEGR1

Chr 1

neuronal growth regulator 1

Also known as: DMML2433, IGLON4, KILON, Ntra

NCBI Gene: 257194 ENSG00000172260 UniProt: Q7Z3B1 OMIM: 613173

NEGR1 encodes a cell adhesion protein that promotes axon sprouting and is involved in synapse assembly and nervous system development. Mutations cause neurodevelopmental disorders with intellectual disability and autism spectrum features. The gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.25).

OMIM ResearchSummary from RefSeq, UniProt

Enables transmembrane transporter binding activity. Acts upstream of or within several processes, including cholesterol homeostasis; protein localization to plasma membrane raft; and regulation of protein stability. Located in late endosome and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM 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

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.992

Z-score 3.80

OE 0.05 (0.02–0.25)

Highly constrained

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

Missense Constraint?

1.64Z-score

OE missense 0.67 (0.58–0.78)

135 obs / 200.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.25)

0≤0.351.4

Missense OE?0.67 (0.58–0.78)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 18.8Missense obs/exp: 135 / 200.2Syn Z: -0.34

Background carrier burden — how many people carry a rare variant somewhere in NEGR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

373 rare PASS variants

Rare truncating (LoF)

1 in 9,800

26 rare PASS variants

Rare synonymous (reference)

1 in 130

196 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEGR1. 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 340	1 in 8,700
South Asian	~43k	1 in 210	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,100	1 in 3,000
Admixed American	~22k	1 in 220	none seen
African / African American	~21k	1 in 340	none seen
East Asian	~20k	1 in 170	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	1 in 360	≈ 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): 6 of 7 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 7.? see exons ↓