Hypotrichosis 14

Summary

Hypotrichosis 14 (MONDO:0032649) is a disease caused by LSS (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LSS (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypotrichosis 14
Mondo ID	MONDO:0032649
OMIM	618275
DOID	DOID:0080582
UMLS	C4748930
MedGen	1648477
GARD	0016335
Is cancer (heuristic)	no

Also known as: HYPT14

Data availability: 12 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hypotrichosis › hypotrichosis 14

Related subtypes (18): hypotrichosis of eyelid, hypotrichosis 2, hypotrichosis 8, congenital hypotrichosis with juvenile macular dystrophy, hypotrichosis 7, hypotrichosis 1, hypotrichosis 6, hypotrichosis 3, hypotrichosis 9, hypotrichosis 10, hypotrichosis 11, hypotrichosis 12, hypotrichosis 13, Marie Unna hereditary hypotrichosis, Basaran Yilmaz syndrome, congenital hypotrichosis milia, hypotrichosis 15, hypotrichosis 16

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

12 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 2 benign/likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1256057	NM_002340.6(LSS):c.647G>A (p.Trp216Ter)	LSS	Pathogenic	criteria provided, multiple submitters, no conflicts
1526304	NM_002340.6(LSS):c.530G>A (p.Arg177Gln)	LSS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
599320	NM_002340.6(LSS):c.743T>C (p.Leu248Pro)	LSS	Pathogenic	no assertion criteria provided
599321	NM_002340.6(LSS):c.304C>G (p.Leu102Val)	LSS	Pathogenic	criteria provided, single submitter
1256056	NM_002340.6(LSS):c.857A>G (p.Tyr286Cys)	LSS	Likely pathogenic	criteria provided, multiple submitters, no conflicts
599319	NM_002340.6(LSS):c.1172T>C (p.Phe391Ser)	LSS	Likely pathogenic	criteria provided, single submitter
221226	NM_002340.6(LSS):c.1762G>A (p.Gly588Ser)	LSS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805095	NM_002340.6(LSS):c.2149_2161del (p.Gly717fs)	LSS	Uncertain significance	criteria provided, multiple submitters, no conflicts
2506958	NM_002340.6(LSS):c.831G>C (p.Arg277Ser)	LSS	Uncertain significance	criteria provided, single submitter
3370480	NM_002340.6(LSS):c.2168A>C (p.Tyr723Ser)	LSS	Uncertain significance	criteria provided, single submitter
1201735	NM_002340.6(LSS):c.181-27dup	LSS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
783885	NM_002340.6(LSS):c.752C>T (p.Ala251Val)	LSS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
LSS	Strong	Autosomal recessive	hypotrichosis 14	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LSS	Orphanet:1366	Autosomal recessive palmoplantar keratoderma and congenital alopecia
LSS	Orphanet:2850	Alopecia-intellectual disability syndrome
LSS	Orphanet:55654	Hypotrichosis simplex
LSS	Orphanet:98994	Total early-onset cataract

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
LSS	HGNC:6708	ENSG00000160285	P48449	Lanosterol synthase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LSS	Lanosterol synthase	Key enzyme in the cholesterol biosynthesis pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LSS	Enzyme (other)	yes	5.4.99.7	Terpene_synthase_CS, Terpenoid_cyclase/PrenylTrfase, Squalene_cyclase

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
mucosa of stomach	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LSS	134	ubiquitous	marker	mucosa of stomach, C1 segment of cervical spinal cord, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LSS	1,562

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LSS	P48449	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Cholesterol biosynthesis	1	1142.0×	0.005	LSS
Lanosterol biosynthesis	1	761.3×	0.005	LSS
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.007	LSS
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.007	LSS
Metabolism of steroids	1	137.6×	0.010	LSS
Metabolism of lipids	1	31.6×	0.037	LSS
Metabolism	1	11.6×	0.086	LSS

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
triterpenoid biosynthetic process	1	16852.0×	2e-04	LSS
steroid biosynthetic process	1	601.9×	0.003	LSS
cholesterol biosynthetic process	1	421.3×	0.003	LSS
regulation of protein stability	1	125.8×	0.008	LSS

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LSS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LSS	46	Binding:45, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LSS	5.4.99.7	Lanosterol synthase

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	1	LSS
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
LSS	46	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.