Cholestasis, progressive familial intrahepatic, 10

Summary

Cholestasis, progressive familial intrahepatic, 10 (MONDO:0030810) is a disease caused by MYO5B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYO5B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cholestasis, progressive familial intrahepatic, 10
Mondo ID	MONDO:0030810
OMIM	619868
UMLS	C5676981
MedGen	1807702
GARD	0025641
Is cancer (heuristic)	no

Also known as: cholestasis, progressive familial intrahepatic, 10 · PFIC10

Data availability: 43 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › progressive familial intrahepatic cholestasis › cholestasis, progressive familial intrahepatic, 10

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, hereditary North American Indian childhood cirrhosis, 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, 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

43 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 8 pathogenic, 6 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 likely pathogenic, 2 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686946	NM_001080467.3(MYO5B):c.[1135C>T;2470C>T]		Pathogenic	no assertion criteria provided
1686942	NM_001080467.3(MYO5B):c.274C>T (p.Arg92Cys)	MYO5B	Pathogenic	no assertion criteria provided
1686943	NM_001080467.3(MYO5B):c.2395C>T (p.Arg799Trp)	MYO5B	Pathogenic	no assertion criteria provided
1686944	NM_001080467.3(MYO5B):c.2414+5G>T	MYO5B	Pathogenic	no assertion criteria provided
1686945	NM_001080467.3(MYO5B):c.356A>G (p.Tyr119Cys)	MYO5B	Pathogenic	no assertion criteria provided
1686957	NM_001080467.3(MYO5B):c.3538-1G>A	MYO5B	Pathogenic	no assertion criteria provided
1686959	NM_001080467.3(MYO5B):c.1021C>T (p.Gln341Ter)	MYO5B	Pathogenic	no assertion criteria provided
1686961	NM_001080467.3(MYO5B):c.1860dup (p.Met621fs)	MYO5B	Pathogenic	criteria provided, single submitter
4074745	NM_001080467.3(MYO5B):c.1175T>C (p.Met392Thr)	MYO5B	Likely pathogenic	criteria provided, single submitter
4074746	NM_001080467.3(MYO5B):c.3000del (p.Ile1001fs)	MYO5B	Likely pathogenic	criteria provided, single submitter
632299	NM_001080467.3(MYO5B):c.4611+2T>C	MYO5B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
594845	NM_001080467.3(MYO5B):c.4240G>A (p.Glu1414Lys)	LOC126862745	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1081281	NM_001080467.3(MYO5B):c.2306T>A (p.Ile769Asn)	MYO5B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1510451	NM_001080467.3(MYO5B):c.2470C>T (p.Arg824Cys)	MYO5B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3255328	NM_001080467.3(MYO5B):c.266T>C (p.Leu89Ser)	MYO5B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
327026	NM_001080467.3(MYO5B):c.3488T>G (p.Leu1163Arg)	MYO5B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891724	NM_001080467.3(MYO5B):c.-93C>T	MYO5B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038856	NM_001080467.3(MYO5B):c.2995C>T (p.Arg999Cys)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1349914	NM_001080467.3(MYO5B):c.3738G>C (p.Gln1246His)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383089	NM_001080467.3(MYO5B):c.1404G>A (p.Ser468=)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1436086	NM_001080467.3(MYO5B):c.1325T>C (p.Phe442Ser)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1485987	NM_001080467.3(MYO5B):c.1201C>T (p.Arg401Cys)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1686960	NM_001080467.3(MYO5B):c.1463T>C (p.Ile488Thr)	MYO5B	Uncertain significance	criteria provided, single submitter
1705511	NM_001080467.3(MYO5B):c.999G>T (p.Leu333Phe)	MYO5B	Uncertain significance	criteria provided, single submitter
2242082	NM_001080467.3(MYO5B):c.4655A>G (p.Asn1552Ser)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
327003	NM_001080467.3(MYO5B):c.5041G>T (p.Val1681Leu)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3297886	NM_001080467.3(MYO5B):c.548T>C (p.Val183Ala)	MYO5B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377602	NM_001080467.3(MYO5B):c.1572G>T (p.Trp524Cys)	MYO5B	Uncertain significance	criteria provided, single submitter
3391182	NM_001080467.3(MYO5B):c.770G>A (p.Arg257Lys)	MYO5B	Uncertain significance	criteria provided, single submitter
3391183	NM_001080467.3(MYO5B):c.3276G>A (p.Lys1092=)	MYO5B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
MYO5B	Strong	Autosomal recessive	cholestasis, progressive familial intrahepatic, 10	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO5B	Orphanet:2290	Microvillus inclusion disease
MYO5B	Orphanet:480491	MYO5B-related progressive familial intrahepatic cholestasis
MYO5B	Orphanet:79306	Progressive familial intrahepatic cholestasis type 1

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
MYO5B	HGNC:7603	ENSG00000167306	Q9ULV0	Unconventional myosin-Vb	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO5B	Unconventional myosin-Vb	May be involved in vesicular trafficking via its association with the CART complex.

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)
MYO5B	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Dilute_dom

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
ileal mucosa	1
jejunal mucosa	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO5B	228	broad	marker	ileal mucosa, lower esophagus mucosa, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO5B	3,604

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO5B	Q9ULV0	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Aquaporin-mediated transport	1	368.4×	0.006	MYO5B
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.006	MYO5B
Transport of small molecules	1	25.1×	0.040	MYO5B

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
renal water homeostasis	1	510.7×	0.012	MYO5B
endosomal transport	1	244.2×	0.012	MYO5B
actin filament organization	1	118.7×	0.013	MYO5B
vesicle-mediated transport	1	96.3×	0.013	MYO5B
endocytosis	1	95.2×	0.013	MYO5B
protein transport	1	43.9×	0.023	MYO5B

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
MYO5B	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	MYO5B

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)
MYO5B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.