Hereditary mucoepithelial dysplasia

Summary

Hereditary mucoepithelial dysplasia (MONDO:0008017) is a disease caused by SREBF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: SREBF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12
• Phenotypes (HPO): 18

Clinical features

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000212	Gingival overgrowth	Very frequent (80-99%)
HP:0000221	Furrowed tongue	Very frequent (80-99%)
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000962	Hyperkeratosis	Very frequent (80-99%)
HP:0001131	Corneal dystrophy	Very frequent (80-99%)
HP:0001596	Alopecia	Very frequent (80-99%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0002213	Fine hair	Very frequent (80-99%)
HP:0002575	Tracheoesophageal fistula	Very frequent (80-99%)
HP:0008070	Sparse hair	Very frequent (80-99%)
HP:0012732	Anorectal anomaly	Very frequent (80-99%)
HP:0000008	Abnormal morphology of female internal genitalia	Frequent (30-79%)
HP:0000014	Abnormality of the bladder	Frequent (30-79%)
HP:0000119	Abnormality of the genitourinary system	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0002206	Pulmonary fibrosis	Frequent (30-79%)
HP:0000790	Hematuria	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary mucoepithelial dysplasia
Mondo ID	MONDO:0008017
MeSH	C536476
OMIM	158310
Orphanet	1839
ICD-11	1167609602
SNOMED CT	403442005
UMLS	C1274795
MedGen	220887
GARD	0005427
Is cancer (heuristic)	no

Also known as: HMD · mucoepithelial dysplasia, hereditary · Urban-Schosser-Spohn syndrome

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

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary skin disorder › hereditary mucoepithelial dysplasia

Related subtypes (113): alopecia, isolated, reticulate pigment disorder, dyschromatosis universalis hereditaria, psoriasis, porokeratosis, hereditary papulotranslucent acrokeratoderma, acrokeratosis verruciformis, Tietz syndrome, familial primary localized cutaneous amyloidosis, isolated anhidrosis with normal sweat glands, aplasia cutis congenita, blue rubber bleb nevus, Darier disease, dermatosis papulosa nigra, autosomal dominant vibratory urticaria, absence of fingerprints-congenital milia syndrome, pilomatrixoma, spinocerebellar ataxia type 34, isolated congenital adermatoglyphia, isolated hyperchlorhidrosis, hyperkeratosis-hyperpigmentation syndrome, hyperpigmentation with or without hypopigmentation, familial progressive, lichen sclerosus et atrophicus, lichen planus, familial, monilethrix, schwannomatosis, nevus, epidermal, familial multiple nevi flammei, linear nevus sebaceous syndrome, progressive osseous heteroplasia, Hailey-Hailey disease, piebaldism, familial pityriasis rubra pilaris, scalp defects-postaxial polydactyly syndrome, seborrheic keratosis, Sneddon syndrome, sebocystomatosis, stiff skin syndrome, familial multiple discoid fibromas, urticaria, aquagenic, urticaria, familial localized heat, vasculitis, lymphocytic, nodular, VPS13A-related neurodegenerative disease, acrogeria, anhidrosis, familial generalized, with abnormal or absent sweat glands, deafness, congenital, with total albinism, epidermodysplasia verruciformis, combined immunodeficiency with skin granulomas, lipoid proteinosis, neurocutaneous melanocytosis, neutrophil actin dysfunction, albinism-hearing loss syndrome, X-linked reticulate pigmentary disorder, CHILD syndrome, linear skin defects with multiple congenital anomalies, dermatitis herpetiformis, familial, keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome, H syndrome, hydroa vacciniforme, familial, poikiloderma with neutropenia, acne, infundibulocystic basal cell carcinoma, Becker nevus syndrome, generalized basaloid follicular hamartoma syndrome, sweet syndrome, MEDNIK syndrome, seborrhea-like dermatitis with psoriasiform elements, DK1-congenital disorder of glycosylation, body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency, Legius syndrome, CLOVES syndrome, encephalocraniocutaneous lipomatosis, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, hereditary sclerosing poikiloderma with tendon and pulmonary involvement, cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis, skin creases, congenital symmetric circumferential, 2, nevus comedonicus syndrome, severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome, chronic mucocutaneous candidiasis, segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome, hereditary mucosal leukokeratosis, inherited ichthyosis, hereditary photodermatosis, Cowden disease, juvenile hyaline fibromatosis, osteopathia striata-pigmentary dermopathy-white forelock syndrome, syndromic oculocutaneous albinism, phakomatosis pigmentokeratotica, neonatal inflammatory skin and bowel disease, lamellar ichthyosis, PENS syndrome, familial multiple fibrofolliculoma, autosomal recessive cutis laxa type 2A, familial chilblain lupus, familial keratoacanthoma, keratosis pilaris atrophicans, Cobb syndrome, oculocutaneous albinism, hereditary palmoplantar keratoderma, inherited epidermolysis bullosa, ectodermal dysplasia syndrome, subcutaneous panniculitis-like T-cell lymphoma, hereditary angioedema, hereditary lipodystrophy, X-linked chondrodysplasia punctata 2, multiple benign circumferential skin creases on limbs 1, lentigo, familial acne inversa, familial acanthosis nigricans, large congenital melanocytic nevus, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, inflammatory poikiloderma with hair abnormalities and acral keratoses

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:

7 uncertain significance, 3 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
932243	NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys)	SREBF1	Pathogenic	criteria provided, multiple submitters, no conflicts
3065078	NM_004176.5(SREBF1):c.91+1G>C	SREBF1	Likely pathogenic	criteria provided, single submitter
4277558	NM_004176.5(SREBF1):c.406_418del (p.Thr136fs)	SREBF1	Likely pathogenic	criteria provided, single submitter
981495	NM_004176.5(SREBF1):c.1580G>A (p.Arg527His)	SREBF1	Likely pathogenic	criteria provided, single submitter
2456472	NM_004176.5(SREBF1):c.457G>A (p.Ala153Thr)	SREBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2363509	NM_004176.5(SREBF1):c.835G>A (p.Gly279Arg)	SREBF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892556	NM_004176.5(SREBF1):c.1122A>C (p.Gln374His)	SREBF1	Uncertain significance	criteria provided, single submitter
3892557	NM_004176.5(SREBF1):c.265G>A (p.Gly89Arg)	SREBF1	Uncertain significance	criteria provided, single submitter
3892558	NM_004176.5(SREBF1):c.2717G>A (p.Arg906Gln)	SREBF1	Uncertain significance	criteria provided, single submitter
3892560	NM_004176.5(SREBF1):c.3322C>T (p.Arg1108Cys)	SREBF1	Uncertain significance	criteria provided, single submitter
3892561	NM_004176.5(SREBF1):c.41C>A (p.Ala14Glu)	SREBF1	Uncertain significance	criteria provided, single submitter
3892562	NM_004176.5(SREBF1):c.991A>G (p.Ile331Val)	SREBF1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · 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
SREBF1	Strong	Autosomal dominant	hereditary mucoepithelial dysplasia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SREBF1	Orphanet:388	Hirschsprung disease

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
SREBF1	HGNC:11289	ENSG00000072310	P36956	Sterol regulatory element-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SREBF1	Sterol regulatory element-binding protein 1	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane.

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)
SREBF1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf

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
left adrenal gland	1
left adrenal gland cortex	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SREBF1	172	ubiquitous	marker	left adrenal gland, right adrenal gland, left adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SREBF1	4,089

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SREBF1	P36956	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	1	1268.9×	0.005	SREBF1
Cholesterol biosynthesis	1	1142.0×	0.005	SREBF1
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis	1	1142.0×	0.005	SREBF1
R-HSA-1368082	1	713.8×	0.006	SREBF1
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	1	407.9×	0.006	SREBF1
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	380.7×	0.006	SREBF1
R-HSA-400253	1	346.1×	0.006	SREBF1
FOXO-mediated transcription	1	335.9×	0.006	SREBF1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.006	SREBF1
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.007	SREBF1
Metabolism of steroids	1	137.6×	0.012	SREBF1
Transcriptional regulation of white adipocyte differentiation	1	129.8×	0.012	SREBF1
PPARA activates gene expression	1	94.4×	0.015	SREBF1
Metabolism of lipids	1	31.6×	0.041	SREBF1
RNA Polymerase II Transcription	1	22.5×	0.053	SREBF1
Gene expression (Transcription)	1	17.8×	0.063	SREBF1
Generic Transcription Pathway	1	15.1×	0.070	SREBF1
Metabolism	1	11.6×	0.086	SREBF1

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
regulation of heart rate by chemical signal	1	5617.3×	0.003	SREBF1
negative regulation of triglyceride metabolic process	1	4213.0×	0.003	SREBF1
response to fructose	1	2407.4×	0.003	SREBF1
obsolete regulation of protein targeting to mitochondrion	1	2106.5×	0.003	SREBF1
regulation of fatty acid metabolic process	1	1872.4×	0.003	SREBF1
SREBP signaling pathway	1	1872.4×	0.003	SREBF1
response to glucagon	1	1685.2×	0.003	SREBF1
positive regulation of triglyceride biosynthetic process	1	1296.3×	0.003	SREBF1
regulation of mitophagy	1	1203.7×	0.003	SREBF1
positive regulation of cholesterol biosynthetic process	1	1123.5×	0.003	SREBF1
lipid biosynthetic process	1	991.3×	0.003	SREBF1
cellular response to fatty acid	1	702.2×	0.004	SREBF1
response to cAMP	1	510.7×	0.004	SREBF1
response to food	1	495.6×	0.004	SREBF1
response to progesterone	1	495.6×	0.004	SREBF1
negative regulation of insulin secretion	1	495.6×	0.004	SREBF1
insulin secretion	1	432.1×	0.005	SREBF1
cholesterol biosynthetic process	1	421.3×	0.005	SREBF1
response to retinoic acid	1	383.0×	0.005	SREBF1
mRNA transcription by RNA polymerase II	1	330.4×	0.005	SREBF1
response to nutrient	1	295.6×	0.005	SREBF1
positive regulation of miRNA transcription	1	290.6×	0.005	SREBF1
response to glucose	1	255.3×	0.006	SREBF1
circadian rhythm	1	244.2×	0.006	SREBF1
insulin receptor signaling pathway	1	221.7×	0.006	SREBF1
lung development	1	198.3×	0.007	SREBF1
cellular response to starvation	1	193.7×	0.007	SREBF1
fat cell differentiation	1	181.2×	0.007	SREBF1
response to ethanol	1	146.5×	0.008	SREBF1
regulation of protein stability	1	125.8×	0.009	SREBF1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SREBF1	CALCIFEDIOL ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SREBF1	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CALCIFEDIOL ANHYDROUS	4	SREBF1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SREBF1	17	Binding:17

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
CALCIFEDIOL ANHYDROUS	4	SREBF1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SREBF1
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.