ITIH2

Chr 10

inter-alpha-trypsin inhibitor heavy chain 2

Also known as: H2P, ITI-HC2, SHAP

The inter-alpha-trypsin inhibitors (ITI) are a family of structurally related plasma serine protease inhibitors involved in extracellular matrix stabilization and in prevention of tumor metastasis. The ITI family contains multiple proteins made up of a light chain (see MIM 176870) and a variable number of heavy chains (Salier et al., 1987 [PubMed 2446322]; Himmelfarb et al., 2004 [PubMed 14744536]).[supplied by OMIM, Nov 2009]

0
Active trials
17
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.09
LOEUF
DN
Mechanism· predicted
Clinical SummaryITIH2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.000
Z-score 1.04
OE 0.84 (0.651.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.61Z-score
OE missense 0.93 (0.861.00)
495 obs / 534.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.651.09)
00.351.4
Missense OE0.93 (0.861.00)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 39 / 46.6Missense obs/exp: 495 / 534.9Syn Z: 0.34
DN
0.6356th %ile
GOF
0.5367th %ile
LOF
0.3550th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ITIH2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC