IFNGR1

Chr 6ARAD

interferon gamma receptor 1

Also known as: CD119, IFNGR, IMD27A, IMD27B

NCBI Gene: 3459 ENSG00000027697 UniProt: P15260

This gene (IFNGR1) encodes the ligand-binding chain (alpha) of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. A genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection. In addition, defects in IFNGR1 are a cause of mendelian susceptibility to mycobacterial disease, also known as familial disseminated atypical mycobacterial infection. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{H. pylori infection, susceptibility to}MIM #600263

{Hepatitis B virus infection, susceptibility to}MIM #610424

{Tuberculosis infection, protection against}MIM #607948

{Tuberculosis, susceptibility to}MIM #607948

Immunodeficiency 27A, mycobacteriosis, ARMIM #209950

Immunodeficiency 27B, mycobacteriosis, ADMIM #615978

440

ClinVar variants

Pathogenic / LP

0.02

pLI score

Active trials

Clinical Summary— IFNGR1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

51 Pathogenic / Likely Pathogenic· 245 VUS of 440 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.70LOEUF

pLI 0.016

Z-score 2.46

OE 0.35 (0.19–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.31Z-score

OE missense 0.95 (0.85–1.05)

246 obs / 259.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.19–0.70)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.85–1.05)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88

0≤1.21.6

LoF obs/exp: 6 / 16.9Missense obs/exp: 246 / 259.8Syn Z: 0.95

ClinVar Variant Classifications

440 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41

Likely Pathogenic10

VUS245

Likely Benign117

Benign20

Conflicting7

Pathogenic

Likely Pathogenic

245

VUS

117

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	3	20	0	41
Likely Pathogenic	6	2	2	0	10
VUS	3	213	25	4	245
Likely Benign	0	4	45	68	117
Benign	0	2	15	3	20
Conflicting	—				7
Total	27	224	107	75	440

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

View in ClinVar →

Protein Context — Lollipop Plot

IFNGR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

INTERFERON-GAMMA RECEPTOR 1; IFNGR1

MIM #107470 · *

{H. pylori infection, susceptibility to}

MIM #600263