Kindler syndrome

Summary

Kindler syndrome (MONDO:0008260) is a disease caused by FERMT1 (GenCC Definitive), with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include vehicle.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FERMT1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 193
• Phenotypes (HPO): 41
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		250	Worldwide	Validated
Point prevalence	1-9 / 1 000 000	0.2	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

41 HPO clinical features (Orphanet curated; top 41 by frequency):

HPO ID	Term	Frequency
HP:0000982	Palmoplantar keratoderma	Very frequent (80-99%)
HP:0000992	Cutaneous photosensitivity	Very frequent (80-99%)
HP:0001029	Poikiloderma	Very frequent (80-99%)
HP:0008065	Aplasia/Hypoplasia of the skin	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0010783	Erythema	Very frequent (80-99%)
HP:0100825	Cheilitis	Very frequent (80-99%)
HP:0000230	Gingivitis	Frequent (30-79%)
HP:0000670	Carious teeth	Frequent (30-79%)
HP:0000682	Abnormality of dental enamel	Frequent (30-79%)
HP:0000704	Periodontitis	Frequent (30-79%)
HP:0001000	Abnormality of skin pigmentation	Frequent (30-79%)
HP:0001581	Recurrent skin infections	Frequent (30-79%)
HP:0001741	Phimosis	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002043	Esophageal stricture	Frequent (30-79%)
HP:0002583	Colitis	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0006323	Premature loss of primary teeth	Frequent (30-79%)
HP:0008388	Abnormal toenail morphology	Frequent (30-79%)
HP:0100490	Camptodactyly of finger	Frequent (30-79%)
HP:0100633	Esophagitis	Frequent (30-79%)
HP:0000262	Turricephaly	Occasional (5-29%)
HP:0000509	Conjunctivitis	Occasional (5-29%)
HP:0000656	Ectropion	Occasional (5-29%)
HP:0000772	Abnormal rib morphology	Occasional (5-29%)
HP:0000929	Abnormal skull morphology	Occasional (5-29%)
HP:0000962	Hyperkeratosis	Occasional (5-29%)
HP:0000987	Atypical scarring of skin	Occasional (5-29%)
HP:0001056	Milia	Occasional (5-29%)
HP:0001371	Flexion contracture	Occasional (5-29%)
HP:0001602	Laryngeal stenosis	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002037	Inflammation of the large intestine	Occasional (5-29%)
HP:0002860	Squamous cell carcinoma	Occasional (5-29%)
HP:0004378	Abnormality of the anus	Occasional (5-29%)
HP:0007957	Corneal opacity	Occasional (5-29%)
HP:0010044	Short 4th metacarpal	Occasional (5-29%)
HP:0010047	Short 5th metacarpal	Occasional (5-29%)
HP:0012227	Urethral stricture	Occasional (5-29%)
HP:0100517	Neoplasm of the urethra	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Kindler syndrome
Mondo ID	MONDO:0008260
MeSH	C536321
OMIM	173650
Orphanet	2908
DOID	DOID:0060472
ICD-11	726317303
SNOMED CT	238836000
UMLS	C0406557
MedGen	96060
GARD	0004391
Is cancer (heuristic)	no

Also known as: congenital bullous poikiloderma · Kindler syndrome · KNDLRS · KS · poikiloderma of Kindler

Data availability: 193 ClinVar variants · 6 GenCC gene-disease records.

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 › vesiculobullous skin disease › epidermolysis bullosa › inherited epidermolysis bullosa › Kindler syndrome

Related subtypes (3): epidermolysis bullosa dystrophica, epidermolysis bullosa simplex, junctional epidermolysis bullosa

Subtypes (1): hereditary acrokeratotic poikiloderma, Weary type

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

193 retrieved; paginated sample, class counts are floors:

79 uncertain significance, 41 benign, 28 pathogenic, 14 conflicting classifications of pathogenicity, 11 likely benign, 10 not provided, 6 likely pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1047996	NM_017671.5(FERMT1):c.341C>G (p.Ser114Ter)	FERMT1	Pathogenic	criteria provided, single submitter
1047997	NM_017671.5(FERMT1):c.1264+1G>A	FERMT1	Pathogenic	criteria provided, single submitter
1047998	NM_017671.5(FERMT1):c.1378C>T (p.Gln460Ter)	FERMT1	Pathogenic	criteria provided, single submitter
1048114	NM_017671.5(FERMT1):c.1264+363_1372-602del	FERMT1	Pathogenic	criteria provided, single submitter
1172545	NM_017671.5(FERMT1):c.994C>T (p.Gln332Ter)	FERMT1	Pathogenic	criteria provided, single submitter
1322895	NM_017671.5(FERMT1):c.328C>T (p.Arg110Ter)	FERMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1329491	NM_017671.5(FERMT1):c.1861-1G>A	FERMT1	Pathogenic	criteria provided, single submitter
1341677	NM_017671.5:c.892_893insALU	FERMT1	Pathogenic	no assertion criteria provided
224165	NM_017671.5(FERMT1):c.1198T>C (p.Ser400Pro)	FERMT1	Pathogenic	criteria provided, single submitter
224168	NM_017671.5(FERMT1):c.1867_1869del (p.Ile623del)	FERMT1	Pathogenic	criteria provided, single submitter
224172	NM_017671.4:c.676insC	FERMT1	Pathogenic	no assertion criteria provided
224173	NM_017671.5(FERMT1):c.910G>T (p.Glu304Ter)	FERMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
224183	NC_000020.11:g.6122304_6124256del	FERMT1	Pathogenic	no assertion criteria provided
224184	NM_017671.5(FERMT1):c.850-272_1139+53del	FERMT1	Pathogenic	no assertion criteria provided
224185	g.6116239_6120157del	FERMT1	Pathogenic	no assertion criteria provided
224186	g.6109607_6112272del	FERMT1	Pathogenic	no assertion criteria provided
2444858	NM_017671.5(FERMT1):c.35G>A (p.Trp12Ter)	FERMT1	Pathogenic	criteria provided, single submitter
2713	NM_017671.5(FERMT1):c.385+2T>C	FERMT1	Pathogenic	no assertion criteria provided
2714	NM_017671.5(FERMT1):c.787C>T (p.Gln263Ter)	FERMT1	Pathogenic	criteria provided, single submitter
2715	NM_017671.5(FERMT1):c.1714_1715insA (p.Val572fs)	FERMT1	Pathogenic	no assertion criteria provided
2716	NM_017671.5(FERMT1):c.464del (p.Asn155fs)	FERMT1	Pathogenic	no assertion criteria provided
2717	NM_017671.5(FERMT1):c.811C>T (p.Arg271Ter)	FERMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
2718	NM_017671.5(FERMT1):c.862C>T (p.Arg288Ter)	FERMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
3068631	NM_017671.5(FERMT1):c.1648G>T (p.Glu550Ter)	FERMT1	Pathogenic	criteria provided, single submitter
3382333	NM_017671.5(FERMT1):c.936del (p.Met312fs)	FERMT1	Pathogenic	criteria provided, single submitter
3382334	NM_017671.5(FERMT1):c.277C>T (p.Gln93Ter)	FERMT1	Pathogenic	criteria provided, single submitter
419593	NM_017671.5(FERMT1):c.676dup (p.Gln226fs)	FERMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
419594	NM_017671.5(FERMT1):c.1371+4A>G	FERMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
224182	NM_017671.5(FERMT1):c.1848G>A (p.Trp616Ter)	FERMT1	Likely pathogenic	no assertion criteria provided
2440238	NM_017671.5(FERMT1):c.373del (p.Cys125fs)	FERMT1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
FERMT1	Definitive	Autosomal recessive	Kindler syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FERMT1	Orphanet:2908	Kindler epidermolysis bullosa

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
FERMT1	HGNC:15889	ENSG00000101311	Q9BQL6	Fermitin family homolog 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FERMT1	Fermitin family homolog 1	Involved in cell adhesion.

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)
FERMT1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, FERM_central

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
colonic mucosa	1
gingival epithelium	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FERMT1	235	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FERMT1	861

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FERMT1	Q9BQL6	81.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
negative regulation of timing of anagen	1	16852.0×	0.001	FERMT1
positive regulation of wound healing, spreading of epidermal cells	1	3370.4×	0.002	FERMT1
keratinocyte migration	1	2407.4×	0.002	FERMT1
positive regulation of transforming growth factor beta production	1	2106.5×	0.002	FERMT1
positive regulation of integrin activation	1	1872.4×	0.002	FERMT1
establishment of epithelial cell polarity	1	1203.7×	0.002	FERMT1
positive regulation of cell adhesion mediated by integrin	1	1053.2×	0.002	FERMT1
negative regulation of protein import into nucleus	1	936.2×	0.002	FERMT1
negative regulation of stem cell proliferation	1	842.6×	0.002	FERMT1
positive regulation of cell-matrix adhesion	1	674.1×	0.003	FERMT1
keratinocyte proliferation	1	581.1×	0.003	FERMT1
positive regulation of transforming growth factor beta receptor signaling pathway	1	526.6×	0.003	FERMT1
basement membrane organization	1	510.7×	0.003	FERMT1
cell-matrix adhesion	1	163.6×	0.007	FERMT1
integrin-mediated signaling pathway	1	160.5×	0.007	FERMT1
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.010	FERMT1
negative regulation of gene expression	1	69.1×	0.015	FERMT1
cell adhesion	1	37.5×	0.027	FERMT1

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
FERMT1	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
FERMT1	2	Binding:2

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	FERMT1

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)
FERMT1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04908215	PHASE2	COMPLETED	INM-755 (Cannabinol) Cream for Treatment of Epidermolysis Bullosa
NCT05033574	Not specified	UNKNOWN	The State of Sexual Development in Children With Inherited Epidermolysis Bullosa

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VEHICLE	0	1