Cholestasis, progressive familial intrahepatic, 9

disease

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Also known as PFIC9

Summary

Cholestasis, progressive familial intrahepatic, 9 (MONDO:0030800) is a disease caused by ZFYVE19 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ZFYVE19 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cholestasis, progressive familial intrahepatic, 9
Mondo ID	MONDO:0030800
OMIM	619849
UMLS	C5676973
MedGen	1809292
GARD	0025639
Is cancer (heuristic)	no

Also known as: cholestasis, progressive familial intrahepatic, 9 · PFIC9

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › progressive familial intrahepatic cholestasis › cholestasis, progressive familial intrahepatic, 9

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

10 retrieved; paginated sample, class counts are floors:

6 pathogenic, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686832	NM_001077268.2(ZFYVE19):c.314C>G (p.Ser105Ter)	ZFYVE19	Pathogenic	no assertion criteria provided
1686833	NM_001077268.2(ZFYVE19):c.226A>G (p.Met76Val)	ZFYVE19	Pathogenic	no assertion criteria provided
1686834	NM_001077268.2(ZFYVE19):c.514C>T (p.Arg172Ter)	ZFYVE19	Pathogenic	no assertion criteria provided
1686835	NM_001077268.2(ZFYVE19):c.547C>T (p.Arg183Ter)	ZFYVE19	Pathogenic	no assertion criteria provided
1686836	NM_001077268.2(ZFYVE19):c.379C>T (p.Gln127Ter)	ZFYVE19	Pathogenic	no assertion criteria provided
1686837	NM_001077268.2(ZFYVE19):c.667C>T (p.Arg223Ter)	ZFYVE19	Pathogenic	no assertion criteria provided
3391294	NM_001077268.2(ZFYVE19):c.717+1G>T	ZFYVE19	Likely pathogenic	criteria provided, single submitter
4845728	NM_001077268.2(ZFYVE19):c.122_123insGGGGCAGGGC (p.Glu46fs)	ZFYVE19	Likely pathogenic	criteria provided, single submitter
3064547	NM_001077268.2(ZFYVE19):c.446A>C (p.Tyr149Ser)	ZFYVE19	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064554	NM_001077268.2(ZFYVE19):c.374G>A (p.Cys125Tyr)	ZFYVE19	Uncertain significance	criteria provided, single submitter

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
ZFYVE19	Strong	Autosomal recessive	cholestasis, progressive familial intrahepatic, 9	2

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
ZFYVE19	HGNC:20758	ENSG00000166140	Q96K21	Abscission/NoCut checkpoint regulator	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZFYVE19	Abscission/NoCut checkpoint regulator	Key regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZFYVE19	Transcription factor	no		Znf_FYVE, Znf_FYVE_PHD, Znf_RING/FYVE/PHD

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
C1 segment of cervical spinal cord	1
lower esophagus mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZFYVE19	211	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZFYVE19	1,425

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZFYVE19	Q96K21	69.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
mitotic cytokinesis checkpoint signaling	1	4213.0×	6e-04	ZFYVE19
negative regulation of cytokinesis	1	2407.4×	6e-04	ZFYVE19
midbody abscission	1	732.7×	0.001	ZFYVE19

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
ZFYVE19	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	ZFYVE19

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)
ZFYVE19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ZFYVE19