Portal hypertension, noncirrhotic, 2

Summary

Portal hypertension, noncirrhotic, 2 (MONDO:0030397) is a disease caused by GIMAP5 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: GIMAP5 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	portal hypertension, noncirrhotic, 2
Mondo ID	MONDO:0030397
OMIM	619463
UMLS	C5561948
MedGen	1794158
Is cancer (heuristic)	no

Also known as: NCPH2

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › portal hypertension, noncirrhotic › portal hypertension, noncirrhotic, 2

Related subtypes (1): portal hypertension, noncirrhotic, 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344845	NM_018384.5(GIMAP5):c.667C>T (p.Leu223Phe)	GIMAP1-GIMAP5	Pathogenic/Likely pathogenic	no assertion criteria provided
1344846	NM_018384.5(GIMAP5):c.326C>T (p.Pro109Leu)	GIMAP1-GIMAP5	Pathogenic/Likely pathogenic	no assertion criteria provided
1344844	NM_018384.5(GIMAP5):c.140T>C (p.Ile47Thr)	GIMAP5	Pathogenic/Likely pathogenic	no assertion criteria provided
1188820	NM_018384.5(GIMAP5):c.611T>C (p.Leu204Pro)	GIMAP1-GIMAP5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GIMAP5	Strong	Autosomal recessive	portal hypertension, noncirrhotic, 2	2

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GIMAP5	HGNC:18005	ENSG00000196329	Q96F15	GTPase IMAP family member 5	gencc,clinvar
GIMAP1-GIMAP5	HGNC:51257	ENSG00000281887		GIMAP1-GIMAP5 readthrough	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GIMAP5	GTPase IMAP family member 5	Plays a role in T lymphocyte development and the optimal generation of CD4/CD8 double-positive thymocytes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GIMAP5	Other/Unknown	no		G_AIG1, P-loop_NTPase, GIMA/IAN/Toc
GIMAP1-GIMAP5	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
right lung	1
upper lobe of left lung	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GIMAP5	165	broad	marker	right lung, granulocyte, upper lobe of left lung
GIMAP1-GIMAP5	126		marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GIMAP5	1,560
GIMAP1-GIMAP5	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GIMAP5	Q96F15	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GIMAP5	0	0
GIMAP1-GIMAP5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	GIMAP5, GIMAP1-GIMAP5

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GIMAP5	0	—
GIMAP1-GIMAP5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.