NTSR1

Chr 20

neurotensin receptor 1

Also known as: NTR

NCBI Gene: 4923 ENSG00000101188 UniProt: P30989 OMIM: 162651

Neurotensin receptor 1 is a G-protein coupled receptor that binds the neuropeptide neurotensin and activates phosphatidylinositol-calcium signaling pathways, regulating functions including blood pressure, glucose metabolism, temperature control, pain perception, and intestinal motility. Mutations cause neurodevelopmental disorder with hypotonia, language delay, and malformations, inherited in an autosomal recessive pattern. This gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Neurotensin receptor 1 belongs to the large superfamily of G-protein coupled receptors. NTSR1 mediates the multiple functions of neurotensin, such as hypotension, hyperglycemia, hypothermia, antinociception, and regulation of intestinal motility and secretion. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.37

Clinical Summary— NTSR1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

76 VUS of 98 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.37LOEUF

pLI 0.000

Z-score 0.49

OE 0.86 (0.56–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.42Z-score

OE missense 1.07 (0.97–1.17)

310 obs / 290.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.56–1.37)

0≤0.351.4

Missense OE?1.07 (0.97–1.17)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 13 / 15.1Missense obs/exp: 310 / 290.1Syn Z: 0.66

This gene — mechanism propensity

0.74top 25%

GOF

0.81top 10%

LOF

0.3454th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

VUS76

Likely Benign7

Benign10

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	76	0	0	76
Likely Benign	2	0	5	7
Benign	6	1	3	10
Total	84	1	8	93

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap NTSR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →