Heterotaxy, visceral, 8, autosomal

Summary

Heterotaxy, visceral, 8, autosomal (MONDO:0014967) is a disease caused by PKD1L1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PKD1L1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	heterotaxy, visceral, 8, autosomal
Mondo ID	MONDO:0014967
OMIM	617205
DOID	DOID:0051022
UMLS	C4310668
MedGen	934635
GARD	0025041
Is cancer (heuristic)	no

Also known as: heterotaxy, visceral, 8, autosomal · heterotaxy, visceral, 8, autosomal; HTX8 · HTX8 · PKD1L1 visceral heterotaxy · visceral heterotaxy caused by mutation in PKD1L1

Data availability: 96 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › visceral heterotaxy › heterotaxy, visceral, 8, autosomal

Related subtypes (18): right atrial isomerism, situs inversus, heterotaxy, visceral, 1, X-linked, laterality defects, autosomal dominant, heterotaxy, visceral, 2, autosomal, heterotaxy, visceral, 3, autosomal, heterotaxy, visceral, 4, autosomal, heterotaxy, visceral, 6, autosomal, heterotaxy, visceral, 7, autosomal, dextrocardia, levocardia, heterotaxy, visceral, 9, autosomal, with male infertility, heterotaxy, visceral, 10, autosomal, with male infertility, heterotaxy, visceral, 11, autosomal, with male infertility, heterotaxy, visceral, 5, autosomal, heterotaxy, visceral, 12, autosomal, heterotaxy, visceral, 13, autosomal, heterotaxy, visceral, 14, autosomal

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

96 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 28 benign, 12 likely pathogenic, 10 pathogenic, 8 conflicting classifications of pathogenicity, 6 benign/likely benign, 3 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027701	NM_138295.5(PKD1L1):c.3601C>T (p.Gln1201Ter)	PKD1L1	Pathogenic	criteria provided, multiple submitters, no conflicts
1308445	NM_138295.5(PKD1L1):c.7663C>T (p.Arg2555Ter)	PKD1L1	Pathogenic	criteria provided, multiple submitters, no conflicts
1686969	NM_138295.5(PKD1L1):c.8005C>T (p.Arg2669Ter)	PKD1L1	Pathogenic	criteria provided, single submitter
1928308	NM_138295.5(PKD1L1):c.2332del (p.Gln778fs)	PKD1L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
235796	NM_138295.5(PKD1L1):c.6473+2_6473+3del	PKD1L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501763	NM_138295.5(PKD1L1):c.4039C>T (p.Arg1347Ter)	PKD1L1	Pathogenic	no assertion criteria provided
2501764	NM_138295.5(PKD1L1):c.4798_4799del (p.Gln1600fs)	PKD1L1	Pathogenic	criteria provided, single submitter
2501765	NM_138295.5(PKD1L1):c.1387C>T (p.Gln463Ter)	PKD1L1	Pathogenic	no assertion criteria provided
3046698	NM_138295.5(PKD1L1):c.1279G>T (p.Glu427Ter)	PKD1L1	Pathogenic	criteria provided, single submitter
3054974	NM_138295.5(PKD1L1):c.1058_1059del (p.Lys353fs)	PKD1L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3075706	NM_138295.5(PKD1L1):c.8096_8105del (p.Lys2699fs)	PKD1L1	Pathogenic	criteria provided, single submitter
3336448	NM_138295.5(PKD1L1):c.3011del (p.Ala1004fs)	PKD1L1	Pathogenic	criteria provided, single submitter
873155	NM_138295.5(PKD1L1):c.160+1G>A	PKD1L1	Pathogenic	no assertion criteria provided
1299502	NM_138295.5(PKD1L1):c.4938T>G (p.Tyr1646Ter)	PKD1L1	Likely pathogenic	criteria provided, single submitter
1324916	NM_138295.5(PKD1L1):c.5086_5087del (p.Lys1696fs)	PKD1L1	Likely pathogenic	criteria provided, single submitter
1334059	NM_138295.5(PKD1L1):c.6396G>A (p.Trp2132Ter)	PKD1L1	Likely pathogenic	criteria provided, single submitter
2627390	NM_138295.5(PKD1L1):c.2453+1G>A	PKD1L1	Likely pathogenic	criteria provided, single submitter
2690673	NM_138295.5(PKD1L1):c.6124del (p.His2042fs)	PKD1L1	Likely pathogenic	criteria provided, single submitter
2920785	NM_138295.5(PKD1L1):c.6748C>T (p.Arg2250Ter)	PKD1L1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3064527	NM_138295.5(PKD1L1):c.7011G>A (p.Trp2337Ter)	PKD1L1	Likely pathogenic	criteria provided, single submitter
3382938	NM_138295.5(PKD1L1):c.1529_1530del (p.Ser510fs)	PKD1L1	Likely pathogenic	criteria provided, single submitter
3780390	NM_138295.5(PKD1L1):c.2848dup (p.Arg950fs)	PKD1L1	Likely pathogenic	criteria provided, single submitter
3780391	NM_138295.5(PKD1L1):c.5521G>T (p.Glu1841Ter)	PKD1L1	Likely pathogenic	criteria provided, single submitter
3780393	NM_138295.5(PKD1L1):c.1916_1926del (p.Ser639fs)	PKD1L1	Likely pathogenic	criteria provided, single submitter
4846887	NM_138295.5(PKD1L1):c.7786C>T (p.Arg2596Ter)	PKD1L1	Likely pathogenic	criteria provided, single submitter
1027704	NM_138295.5(PKD1L1):c.6357G>A (p.Glu2119=)	PKD1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2152049	NM_138295.5(PKD1L1):c.2005A>G (p.Ile669Val)	PKD1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
235198	NM_138295.5(PKD1L1):c.5072G>C (p.Cys1691Ser)	PKD1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2431346	NM_138295.5(PKD1L1):c.310G>A (p.Ala104Thr)	PKD1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2434872	NM_138295.5(PKD1L1):c.1606C>T (p.Leu536=)	PKD1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
PKD1L1	Definitive	Autosomal recessive	heterotaxy, visceral, 8, autosomal	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PKD1L1	Orphanet:101063	Situs inversus totalis
PKD1L1	Orphanet:157769	Situs ambiguus

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PKD1L1	HGNC:18053	ENSG00000158683	Q8TDX9	Polycystin-1-like protein 1	gencc,clinvar
PKD1L1-AS1	HGNC:21911	ENSG00000136275	Q9H7B7	Putative uncharacterized protein PKD1L1-AS1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PKD1L1	Polycystin-1-like protein 1	Component of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and G…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PKD1L1	Antibody/Immunoglobulin	yes		PKD_dom, PLAT/LH2_dom, PKD/REJ-like
PKD1L1-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
apex of heart	1
primordial germ cell in gonad	1
buccal mucosa cell	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PKD1L1	150	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, apex of heart, primordial germ cell in gonad
PKD1L1-AS1	79	tissue_specific	yes	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, triceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PKD1L1	571
PKD1L1-AS1	16

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PKD1L1-AS1	Q9H7B7	57.08
PKD1L1	Q8TDX9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
detection of nodal flow	1	5617.3×	7e-04	PKD1L1
detection of mechanical stimulus	1	1203.7×	0.001	PKD1L1
left/right axis specification	1	1203.7×	0.001	PKD1L1
cell-cell adhesion	1	101.5×	0.010	PKD1L1

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
PKD1L1	0	0
PKD1L1-AS1	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	1	PKD1L1
E	Difficult family or no structure, no drug	1	PKD1L1-AS1

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)
PKD1L1	0	—
PKD1L1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.