hereditary North American Indian childhood cirrhosis

Summary

hereditary North American Indian childhood cirrhosis (MONDO:0011497) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 39

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		36	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary North American Indian childhood cirrhosis
Mondo ID	MONDO:0011497
MeSH	C565737
OMIM	604901
Orphanet	168583
ICD-11	1992710077
SNOMED CT	699189004
UMLS	C1858051
MedGen	387974
GARD	0017037
Is cancer (heuristic)	no

Also known as: NAIC · NORTH American Indian childhood cirrhosis

Data availability: 39 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › progressive familial intrahepatic cholestasis › hereditary North American Indian childhood cirrhosis

Related subtypes (15): progressive familial intrahepatic cholestasis type 1, benign recurrent intrahepatic cholestasis type 1, progressive familial intrahepatic cholestasis type 2, progressive familial intrahepatic cholestasis type 3, cholestasis, progressive familial intrahepatic, 4, cholestasis, progressive familial intrahepatic, 5, MYO5B-related progressive familial intrahepatic cholestasis, cholestasis, progressive familial intrahepatic, 6, cholestasis, progressive familial intrahepatic, 7, with or without hearing loss, cholestasis, progressive familial intrahepatic, 8, cholestasis, progressive familial intrahepatic, 9, cholestasis, progressive familial intrahepatic, 10, cholestasis, progressive familial intrahepatic, 11, cholestasis, progressive familial intrahepatic, 12, cholestasis, progressive familial intrahepatic, 13

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

39 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 9 conflicting classifications of pathogenicity, 6 benign, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3194	NM_032830.3(UTP4):c.1693C>T (p.Arg565Trp)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
710240	NM_032830.3(UTP4):c.302G>T (p.Gly101Val)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885207	NM_032830.3(UTP4):c.1165-7T>C	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885208	NM_032830.3(UTP4):c.1183T>C (p.Cys395Arg)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885213	NM_032830.3(UTP4):c.1308C>T (p.Phe436=)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
886105	NM_032830.3(UTP4):c.1536C>T (p.Asn512=)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
887044	NM_032830.3(UTP4):c.531C>T (p.Ser177=)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
888314	NM_032830.3(UTP4):c.846G>A (p.Pro282=)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
888318	NM_032830.3(UTP4):c.1083A>G (p.Gly361=)	UTP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885209	NM_032830.3(UTP4):c.1249C>T (p.Arg417Trp)	UTP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
885212	NM_032830.3(UTP4):c.1287+6T>C	UTP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
886048	NM_032830.3(UTP4):c.-2-3T>C	UTP4	Uncertain significance	criteria provided, single submitter
886102	NM_032830.3(UTP4):c.1376G>A (p.Gly459Glu)	UTP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
886103	NM_032830.3(UTP4):c.1444+6A>C	UTP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
886104	NM_032830.3(UTP4):c.1451T>G (p.Val484Gly)	UTP4	Uncertain significance	criteria provided, single submitter
886106	NM_032830.3(UTP4):c.1610A>G (p.Asn537Ser)	UTP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
886107	NM_032830.3(UTP4):c.1621C>T (p.Leu541Phe)	UTP4	Uncertain significance	criteria provided, single submitter
886108	NM_032830.3(UTP4):c.1677G>T (p.Gln559His)	UTP4	Uncertain significance	criteria provided, single submitter
887041	NM_032830.3(UTP4):c.57C>A (p.Ile19=)	UTP4	Uncertain significance	criteria provided, single submitter
887043	NM_032830.3(UTP4):c.418A>G (p.Asn140Asp)	UTP4	Uncertain significance	criteria provided, single submitter
887046	NM_032830.3(UTP4):c.632G>A (p.Ser211Asn)	UTP4	Uncertain significance	criteria provided, single submitter
887108	NM_032830.3(UTP4):c.1904G>A (p.Arg635Lys)	UTP4	Uncertain significance	criteria provided, single submitter
887110	NM_032830.3(UTP4):c.*67A>C	UTP4	Uncertain significance	criteria provided, single submitter
888312	NM_032830.3(UTP4):c.739-6C>G	UTP4	Uncertain significance	criteria provided, single submitter
888313	NM_032830.3(UTP4):c.754G>T (p.Val252Leu)	UTP4	Uncertain significance	criteria provided, single submitter
888315	NM_032830.3(UTP4):c.871C>T (p.Arg291Cys)	UTP4	Uncertain significance	criteria provided, single submitter
888316	NM_032830.3(UTP4):c.872G>A (p.Arg291His)	UTP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
888317	NM_032830.3(UTP4):c.1002+15C>T	UTP4	Uncertain significance	criteria provided, single submitter
714710	NM_032830.3(UTP4):c.1313G>A (p.Arg438His)	UTP4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
717483	NM_032830.3(UTP4):c.1164+8A>G	UTP4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
UTP4	Supportive	Autosomal recessive	hereditary North American Indian childhood cirrhosis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UTP4	Orphanet:168583	Hereditary North American Indian childhood cirrhosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UTP4	HGNC:1983	ENSG00000141076	Q969X6	U3 small nucleolar RNA-associated protein 4 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UTP4	U3 small nucleolar RNA-associated protein 4 homolog	Ribosome biogenesis factor.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UTP4	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
gastrocnemius	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UTP4	142	ubiquitous	marker	primordial germ cell in gonad, gastrocnemius, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UTP4	2,377

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UTP4	Q969X6	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
rRNA modification in the nucleus and cytosol	1	187.2×	0.011	UTP4
Major pathway of rRNA processing in the nucleolus and cytosol	1	61.7×	0.016	UTP4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maturation of SSU-rRNA	1	766.0×	0.003	UTP4
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	674.1×	0.003	UTP4
ribosomal small subunit biogenesis	1	227.7×	0.006	UTP4
regulation of DNA-templated transcription	1	31.6×	0.032	UTP4

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
UTP4	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	1	UTP4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UTP4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.