Hyperpigmentation with or without hypopigmentation, familial progressive

Summary

Hyperpigmentation with or without hypopigmentation, familial progressive (MONDO:0007771) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperpigmentation with or without hypopigmentation, familial progressive
Mondo ID	MONDO:0007771
OMIM	145250
DOID	DOID:0111373
UMLS	C1840392
MedGen	333550
GARD	0018073
Is cancer (heuristic)	no

Also known as: FPHH · hyperpigmentation with or without hypopigmentation · hyperpigmentation with or without hypopigmentation, familial progressive · hyperpigmentation, familial progressive, 2 · macules, hereditary congenital hypopigmented and hyperpigmented · melanosis, universal

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › skin pigmentation disorder › hyperpigmentation of the skin › familial progressive hyperpigmentation › hyperpigmentation with or without hypopigmentation, familial progressive

Subtypes (1): familial progressive hyper- and hypopigmentation

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

7 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
12813	NM_000899.5(KITLG):c.107A>G (p.Asn36Ser)	KITLG	Pathogenic	no assertion criteria provided
1710166	NM_000899.5(KITLG):c.108T>G (p.Asn36Lys)	KITLG	Pathogenic	no assertion criteria provided
183168	NM_000899.5(KITLG):c.98T>C (p.Val33Ala)	KITLG	Pathogenic	no assertion criteria provided
183169	NM_000899.5(KITLG):c.100A>C (p.Thr34Pro)	KITLG	Pathogenic	no assertion criteria provided
1803991	NM_000899.5(KITLG):c.106A>C (p.Asn36His)	KITLG	Likely pathogenic	criteria provided, single submitter
1708119	NM_000899.5(KITLG):c.320T>A (p.Ile107Lys)	KITLG	Uncertain significance	criteria provided, single submitter
517646	NM_000899.5(KITLG):c.130-11dup	KITLG	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 5 · 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
KITLG	Moderate	Autosomal dominant	hyperpigmentation with or without hypopigmentation, familial progressive	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KITLG	Orphanet:280628	Familial progressive hyper- and hypopigmentation
KITLG	Orphanet:363494	Non-seminomatous germ cell tumor of testis
KITLG	Orphanet:79146	Familial progressive hyperpigmentation
KITLG	Orphanet:895	Waardenburg syndrome type 2
KITLG	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
KITLG	HGNC:6343	ENSG00000049130	P21583	Kit ligand	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KITLG	Kit ligand	Ligand for the receptor-type protein-tyrosine kinase KIT.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KITLG	Other/Unknown	no		SCF, 4_helix_cytokine-like_core

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
cardia of stomach	1
lower lobe of lung	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KITLG	262	ubiquitous	marker	visceral pleura, cardia of stomach, lower lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KITLG	3,075

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KITLG	P21583	6

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
Regulation of KIT signaling	1	601.0×	0.012	KITLG
Signaling by SCF-KIT	1	248.3×	0.013	KITLG
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.013	KITLG
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.014	KITLG
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.014	KITLG
PIP3 activates AKT signaling	1	66.8×	0.016	KITLG
RAF/MAP kinase cascade	1	61.1×	0.016	KITLG

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
positive regulation of myeloid leukocyte differentiation	1	8426.0×	7e-04	KITLG
myeloid leukocyte differentiation	1	5617.3×	7e-04	KITLG
negative regulation of mast cell apoptotic process	1	5617.3×	7e-04	KITLG
melanocyte migration	1	5617.3×	7e-04	KITLG
mast cell migration	1	5617.3×	7e-04	KITLG
positive regulation of hematopoietic progenitor cell differentiation	1	5617.3×	7e-04	KITLG
mast cell apoptotic process	1	4213.0×	7e-04	KITLG
positive regulation of melanocyte differentiation	1	3370.4×	7e-04	KITLG
mast cell proliferation	1	3370.4×	7e-04	KITLG
positive regulation of mast cell proliferation	1	3370.4×	7e-04	KITLG
positive regulation of hematopoietic stem cell proliferation	1	1872.4×	0.001	KITLG
positive regulation of leukocyte migration	1	991.3×	0.002	KITLG
embryonic hemopoiesis	1	991.3×	0.002	KITLG
positive regulation of Ras protein signal transduction	1	887.0×	0.002	KITLG
ectopic germ cell programmed cell death	1	842.6×	0.002	KITLG
extrinsic apoptotic signaling pathway in absence of ligand	1	468.1×	0.003	KITLG
ovarian follicle development	1	391.9×	0.004	KITLG
T cell proliferation	1	383.0×	0.004	KITLG
neural crest cell migration	1	337.0×	0.004	KITLG
positive regulation of T cell proliferation	1	259.3×	0.005	KITLG
hematopoietic progenitor cell differentiation	1	237.3×	0.005	KITLG
Ras protein signal transduction	1	205.5×	0.006	KITLG
male gonad development	1	156.0×	0.007	KITLG
cell adhesion	1	37.5×	0.028	KITLG
positive regulation of cell population proliferation	1	33.6×	0.030	KITLG

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
KITLG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KITLG	1	Binding:1

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	KITLG

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)
KITLG	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.