FERMT1

Summary

FERMT1 (FERM domain containing kindlin 1, HGNC:15889) is a protein-coding gene on chromosome 20p12.3, encoding Fermitin family homolog 1 (Q9BQL6). Involved in cell adhesion.

This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome.

Source: NCBI Gene 55612 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Kindler syndrome (Definitive, ClinGen)
• GWAS associations: 7
• Clinical variants (ClinVar): 634 total — 43 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes
• MANE Select transcript: NM_017671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15889
Approved symbol	FERMT1
Name	FERM domain containing kindlin 1
Location	20p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20116, URP1, KIND1, UNC112A
Ensembl gene	ENSG00000101311
Ensembl biotype	protein_coding
OMIM	607900
Entrez	55612

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000217289, ENST00000378844, ENST00000478194, ENST00000536936, ENST00000699095, ENST00000699096, ENST00000699097, ENST00000699098, ENST00000855451, ENST00000855452, ENST00000855453, ENST00000936598, ENST00000936599, ENST00000936600

RefSeq mRNA: 1 — MANE Select: NM_017671 NM_017671

CCDS: CCDS13098

Canonical transcript exons

ENST00000217289 — 15 exons

Exon	Start	End
ENSE00001172491	6119404	6119572
ENSE00002246075	6122774	6123030
ENSE00003063928	6097524	6097631
ENSE00003072022	6110298	6110511
ENSE00003182279	6094939	6094988
ENSE00003186584	6096902	6097033
ENSE00003459683	6087777	6087883
ENSE00003464971	6074845	6077346
ENSE00003488375	6084040	6084164
ENSE00003494589	6107532	6107634
ENSE00003503725	6112477	6112623
ENSE00003527447	6115811	6116044
ENSE00003528880	6085066	6085287
ENSE00003538687	6088965	6089089
ENSE00003600246	6079436	6079577

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 97.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4009 / max 251.5418, expressed in 1091 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186365	3.4728	916
186370	0.9589	208
186367	0.5866	248
186372	0.5781	175
186366	0.4143	144
186369	0.3432	135
186362	0.2454	107
186363	0.1595	77
186374	0.1414	69
186368	0.1387	62

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	97.02	gold quality
colonic mucosa	UBERON:0000317	96.46	gold quality
gingival epithelium	UBERON:0001949	95.36	gold quality
gingiva	UBERON:0001828	94.32	gold quality
cervix squamous epithelium	UBERON:0006922	93.96	gold quality
hair follicle	UBERON:0002073	92.84	gold quality
rectum	UBERON:0001052	92.70	gold quality
pancreatic ductal cell	CL:0002079	92.68	gold quality
squamous epithelium	UBERON:0006914	92.31	gold quality
upper leg skin	UBERON:0004262	92.21	gold quality
esophagus squamous epithelium	UBERON:0006920	91.09	gold quality
epithelium of esophagus	UBERON:0001976	90.11	gold quality
mucosa of transverse colon	UBERON:0004991	89.22	gold quality
nipple	UBERON:0002030	88.22	gold quality
right adrenal gland cortex	UBERON:0035827	88.21	gold quality
penis	UBERON:0000989	88.00	gold quality
right adrenal gland	UBERON:0001233	87.88	gold quality
secondary oocyte	CL:0000655	87.80	gold quality
ileal mucosa	UBERON:0000331	87.79	gold quality
tongue squamous epithelium	UBERON:0006919	87.58	gold quality
left adrenal gland	UBERON:0001234	87.12	gold quality
adrenal cortex	UBERON:0001235	86.88	gold quality
oral cavity	UBERON:0000167	86.84	gold quality
left adrenal gland cortex	UBERON:0035825	86.81	gold quality
skin of hip	UBERON:0001554	86.62	gold quality
mammalian vulva	UBERON:0000997	86.12	gold quality
upper arm skin	UBERON:0004263	86.00	gold quality
jejunal mucosa	UBERON:0000399	85.70	gold quality
esophagus mucosa	UBERON:0002469	85.44	gold quality
duodenum	UBERON:0002114	85.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	911.02
E-GEOD-125970	yes	12.73
E-ANND-3	yes	10.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting FERMT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-3975	99.62	65.97	697

Literature-anchored findings (GeneRIF, showing 40)

• kindlerin has a role in mediating cell processes that depend on integrins (PMID:14634021)
• loss-of-function KIND1 mutations demonstrate the importance of kindlin-1 in maintaining epithelial integrity (PMID:14962093)
• Kindlin-1 is considered to be a component in the linkage of the actin cytoskeleton to the extracellular matrix and as such is proposed to have both structural and cell-signalling functions. Review. (PMID:15927810)
• Mutated at intron 13 in Kindler syndrome. (PMID:16051467)
• The abundance of repetitive elements in intronic regions of KIND1, together with the identification of a large deletion, suggests that genomic rearrangements could be responsible for a significant proportion of Kindler syndrome cases (PMID:16675959)
• Kindlin-1 has roles in regulation of polarity, proliferation, and motility of epidermal keratinocytes (PMID:17012746)
• Kindlin-1 links the actin cytoskeleton to the extracellular matrix and is supposed to have cell-signaling functions owing to different functional domains. (PMID:17178989)
• analysis of KIND1 gene mutations in Kindler syndrome [case reports] (PMID:17460733)
• The KIND1 mutation c.67insC represents the most common recurrent pathogenic gene mutation in patients with KS. (PMID:17916195)
• Two patients with Kindler Syndrome have mutations in KIND-1. In patient 1, there was a duplication of cytosine at position 676 in exon 5 of kindlin-1 mRNA. In patient 2, a novel mutation of exon 3 of KIND1 gene c.170C>A. (PMID:17989907)
• Loss-of-function mutations in KIND1 result in marked variability in kindlin-1 immunolabeling in Kindler syndrome skin, which is mirrored by similar changes in kindlin-2 and migfilin immunoreactivity. (PMID:18528435)
• a splice site mutation in the first position of intron 13 of the FERMT1 gene caused skipping of exon 13. (PMID:18652585)
• A novel large FERMT1 (KIND1) gene deletion in Kindler syndrome. (PMID:18835760)
• skin changes on the extremities, face, and neck, including hyper- and hypopigmentation, atrophy, and telangiectasia in Kindler syndrome (PMID:19200189)
• Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects (PMID:19240021)
• The study identified a novel large deletion mutation g.63601_66617del, which expanded the FERMT1 mutation repertoire. (PMID:19292718)
• This study provides evidence that fermitin family homolog-1 is implicated in integrin activation. (PMID:19762710)
• Kindlin-1 forms molecular complexes with beta1 integrin, alpha-actinin, migfilin, and focal adhesion kinase and regulates cell shape and migration by controlling lamellipodia formation. (PMID:19762715)
• The authors demonstrate that the F0 domain of kindlin-1 is required for the ability of kindlin-1 to support talin-induced alphaIIbbeta3 integrin activation and for the localization of kindlin-1 to focal adhesions. (PMID:19804783)
• cellular functions and possible clinical relevance of kindlin-1 [REVIEW] (PMID:19854292)
• Null mutations in FERMT1 result in skin blistering from birth and early childhood progressive poikiloderma, mucosal fragility, and increased risk of cancer (PMID:19945623)
• A novel mutation in the FERMT1 gene in a Spanish family with Kindler’s syndrome is reported. (PMID:20028441)
• In summary, we have described a recurrent splice-site deletion mutation in KIND1 in Kindler syndrome. (PMID:21146372)
• FERMT1 is a novel prognostic factor for colon carcinoma. (PMID:21220475)
• Induction of phenotype modifying cytokines by FERMT1 mutations (PMID:21309038)
• Describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phenotype correlation in this disorder. (PMID:21336475)
• The phenotype of kindlin-1-deficient cells can be modulated by regulating kindlin-2 gene expression and vice versa. (PMID:21356350)
• Kindlin-1 expression in breast tumors is associated with lung metastasis and lung metastasis-free survival through regulation of TGF-beta signaling. Kindlin-1-silencing prevented tumor growth and lung metastasis in mice. (PMID:21832234)
• There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications in Kindler syndrome ( FERMT1 ) (PMID:21936020)
• Direct sequencing of the FERMT1 gene revealed a homozygous insertion of cytosine at position 676 (c.676insC) in exon 5 in seven patients. (PMID:22220914)
• Kindlin-1 and Kindlin-2 have opposite roles in lung cancers (PMID:23209705)
• the results of this study indicate that FERMT1 is expressed specifically in colon carcinoma cells, and has roles in matrix invasion and cell growth (PMID:23267142)
• Individuals with Kindler syndrome (KS) have loss-of-function mutations in the FERMT1 gene (PMID:23278235)
• Kindlin-1 expression is involved in the progression of pancreatic cancer via enhancement of cell migration and invasion. (PMID:23440354)
• Whereas both Integrin-linked kinase (Ilk) and Kindlin-1 cooperate with Integrin alpha3beta1 to resist trauma-induced epidermal defects, Kindlin-1 and Ilk, surprisingly, do not act synergistically but in parallel. (PMID:23549420)
• Data uncover a role for kindlin-1 in the regulation of integrin trafficking and adhesion turnover. (PMID:23776470)
• Short interfering RNA-mediated depletion of Kindlin-1 increases formation of abnormal mitotic spindles which is dependent on the ability of Kindlin-1 to bind integrins and Polo-like kinase 1-mediated Kindlin-1 phosphorylation. (PMID:23804033)
• C-terminal LIM domains of migfilin dictate its focal adhesion localization, and these domains mediate an interaction with kindlin in vitro and in cells, demonstrating that kindlin is important for normal migfilin dynamics. (PMID:24165133)
• We identified a novel mutation in FERMT1. These data are in agreement with the fact that the majority of KS-causing mutations in FERMT1 lead to premature termination of translation and to loss of kindlin-1 function in Kindler sysndrome (PMID:24635080)
• we show that a certain number of KS patients may harbor FERMT1 transcriptional regulatory mutations which are not routinely detected. (PMID:25156791)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fermt1	ENSDARG00000052652
mus_musculus	Fermt1	ENSMUSG00000027356
rattus_norvegicus	Fermt1	ENSRNOG00000021274
drosophila_melanogaster	Fit1	FBGN0035498
drosophila_melanogaster	Fit2	FBGN0036688
caenorhabditis_elegans		WBGENE00006836

Paralogs (2): FERMT2 (ENSG00000073712), FERMT3 (ENSG00000149781)

Protein

Protein identifiers

Fermitin family homolog 1 — Q9BQL6 (reviewed: Q9BQL6)

Alternative names: Kindlerin, Kindlin syndrome protein, Kindlin-1, Unc-112-related protein 1

All UniProt accessions (3): Q9BQL6, A0A8V8TN73, G3V1L6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in cell adhesion. Contributes to integrin activation. When coexpressed with talin, potentiates activation of ITGA2B. Required for normal keratinocyte proliferation. Required for normal polarization of basal keratinocytes in skin, and for normal cell shape. Required for normal adhesion of keratinocytes to fibronectin and laminin, and for normal keratinocyte migration to wound sites. May mediate TGF-beta 1 signaling in tumor progression.

Subunit / interactions. Interacts with the cytoplasmic domain of integrins ITGB1 and ITGB3.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Focal adhesion. Cell projection. Ruffle membrane.

Tissue specificity. Expressed in brain, skeletal muscle, kidney, colon, adrenal gland, prostate, and placenta. Weakly or not expressed in heart, thymus, spleen, liver, small intestine, bone marrow, lung and peripheral blood leukocytes. Overexpressed in some colon and lung tumors. In skin, it is localized within the epidermis and particularly in basal keratocytes. Not detected in epidermal melanocytes and dermal fibroblasts.

Disease relevance. Kindler syndrome (KNDLRS) [MIM:173650] An autosomal recessive skin disorder characterized by skin blistering, photosensitivity, progressive poikiloderma, and extensive skin atrophy. Additional clinical features include gingival erosions, ocular, esophageal, gastrointestinal and urogenital involvement, and an increased risk of mucocutaneous malignancy. The disease is caused by variants affecting the gene represented in this entry. Although most FERMT1 mutations are predicted to lead to premature termination of translation, and to loss of FERMT1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications.

Domain organisation. The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain. The FERM domain contains the subdomains F1, F2 and F3. It is preceded by a F0 domain with a ubiquitin-like fold. The F0 domain is required for integrin activation and for localization at focal adhesions.

Induction. By TGFB1.

Similarity. Belongs to the kindlin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BQL6-1	1	yes
Q9BQL6-2	2
Q9BQL6-3	3
Q9BQL6-4	4

RefSeq proteins (1): NP_060141* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR035963	FERM_2	Homologous_superfamily
IPR037837	PH_Kindlin/fermitin	Domain
IPR037843	Kindlin/fermitin	Family
IPR040790	Kindlin_2_N	Domain

Pfam: PF00373, PF18124

UniProt features (21 total): sequence variant 8, splice variant 5, modified residue 3, domain 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQL6-F1	81.14	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 170, 179, 361

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 377 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, JAEGER_METASTASIS_DN, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GOBP_KERATINOCYTE_PROLIFERATION, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOCC_RUFFLE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (19): positive regulation of cell-matrix adhesion (GO:0001954), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), negative regulation of gene expression (GO:0010629), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), positive regulation of integrin activation (GO:0033625), positive regulation of cell adhesion mediated by integrin (GO:0033630), negative regulation of protein import into nucleus (GO:0042308), keratinocyte proliferation (GO:0043616), keratinocyte migration (GO:0051546), negative regulation of timing of anagen (GO:0051886), positive regulation of transforming growth factor beta production (GO:0071636), basement membrane organization (GO:0071711), negative regulation of canonical Wnt signaling pathway (GO:0090090), establishment of epithelial cell polarity (GO:0090162), positive regulation of wound healing, spreading of epidermal cells (GO:1903691), negative regulation of stem cell proliferation (GO:2000647), positive regulation of cell migration (GO:0030335)

GO Molecular Function (2): integrin binding (GO:0005178), actin filament binding (GO:0051015)

GO Cellular Component (11): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), cell junction (GO:0030054), ruffle membrane (GO:0032587), cell periphery (GO:0071944), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein-containing complex binding	2
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
cellular process	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
positive regulation of protein-containing complex assembly	1
integrin activation	1
regulation of integrin activation	1
cell adhesion mediated by integrin	1
regulation of cell adhesion mediated by integrin	1
positive regulation of cell adhesion	1
protein import into nucleus	1
regulation of protein import into nucleus	1
negative regulation of nucleocytoplasmic transport	1
negative regulation of intracellular protein transport	1
negative regulation of protein localization to nucleus	1
epithelial cell proliferation	1
epithelial cell migration	1
anagen	1
negative regulation of hair follicle maturation	1
regulation of timing of anagen	1
positive regulation of cytokine production	1
transforming growth factor beta production	1
regulation of transforming growth factor beta production	1
extracellular matrix organization	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
establishment of cell polarity	1
positive regulation of cell migration	1

Protein interactions and networks

STRING

798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FERMT1	ILK	P57043	789
FERMT1	FBLIM1	Q8WUP2	787
FERMT1	PLEK2	Q9NYT0	764
FERMT1	PLEK	P08567	756
FERMT1	VCL	P18206	729
FERMT1	ITGB6	P18564	582
FERMT1	COL7A1	Q02388	581
FERMT1	COL17A1	Q9UMD9	581
FERMT1	TCF12	Q99081	549
FERMT1	RDX	P35241	534
FERMT1	TLN2	Q9Y4G6	529
FERMT1	TLN1	Q9Y490	521
FERMT1	TGM5	O43548	513
FERMT1	MSN	P26038	500
FERMT1	EZR	P15311	490

IntAct

17 interactions, top by confidence:

A	B	Type	Score
FERMT1	ABRAXAS2	psi-mi:“MI:0915”(physical association)	0.400
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
FERMT1	TARSL2	psi-mi:“MI:0914”(association)	0.350
E2F1	CLIC1	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
FERMT1	TARS3	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
C1QTNF1	PLOD2	psi-mi:“MI:0914”(association)	0.350
SNW1		psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350
LAMP1	PIPSL	psi-mi:“MI:2364”(proximity)	0.270
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TRABD2B	CD99L2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (46): CACYBP (Co-fractionation), RNASEH2B (Co-fractionation), SBDS (Co-fractionation), SKIV2L (Co-fractionation), TCEB2 (Co-fractionation), TTC37 (Co-fractionation), FERMT1 (Affinity Capture-MS), FERMT1 (Affinity Capture-MS), FERMT1 (Affinity Capture-MS), FERMT1 (Affinity Capture-MS), FERMT1 (Proximity Label-MS), FERMT2 (Affinity Capture-MS), FERMT3 (Affinity Capture-MS), MAGI3 (Affinity Capture-MS), ITPA (Affinity Capture-MS)

ESM2 similar proteins: A1L2W9, B2RQE8, B5XG43, G9CGD6, O08969, O88387, P59113, Q0V987, Q0VC85, Q1KKW7, Q1KKZ1, Q32LP0, Q3UUV5, Q3ZBA3, Q4V7G1, Q503L1, Q53GA4, Q5FVW6, Q5PQT7, Q5R8M5, Q5U597, Q5XGP7, Q5ZL23, Q6P0G8, Q6PG29, Q7Z628, Q7Z6J4, Q80VL0, Q80YS6, Q86UX7, Q86WV1, Q8AW35, Q8BY35, Q8IZC4, Q8K1B8, Q8N556, Q8VH46, Q91ZM9, Q91ZT5, Q925E0

Diamond homologs: A0A3G2LGI8, F1REV3, P0CE94, P26039, P54939, P59113, Q18685, Q54EW0, Q5R8M5, Q71LX4, Q9BQL6, Q9P6L5, Q9Y490, Q9Y4G6, F1Q8X5, Q32LP0, Q86UX7, Q8CIB5, Q8K1B8, Q96AC1, Q9VZI3, P0CE95

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CUL9	“down-regulates quantity by destabilization”	FERMT1	ubiquitination
CyclinB/CDK1	“down-regulates quantity by destabilization”	FERMT1	phosphorylation
hsa-mir-146a-5p	“down-regulates quantity by repression”	FERMT1	“post transcriptional regulation”
FERMT1	“up-regulates activity”	FBLIM1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

634 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	13
Uncertain significance	247
Likely benign	173
Benign	113

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047996	NM_017671.5(FERMT1):c.341C>G (p.Ser114Ter)	Pathogenic
1047997	NM_017671.5(FERMT1):c.1264+1G>A	Pathogenic
1047998	NM_017671.5(FERMT1):c.1378C>T (p.Gln460Ter)	Pathogenic
1048114	NM_017671.5(FERMT1):c.1264+363_1372-602del	Pathogenic
1172545	NM_017671.5(FERMT1):c.994C>T (p.Gln332Ter)	Pathogenic
1322895	NM_017671.5(FERMT1):c.328C>T (p.Arg110Ter)	Pathogenic
1329491	NM_017671.5(FERMT1):c.1861-1G>A	Pathogenic
1341677	NM_017671.5:c.892_893insALU	Pathogenic
1400691	NM_017671.5(FERMT1):c.1277del (p.Val426fs)	Pathogenic
1452763	NM_017671.5(FERMT1):c.678dup (p.Ser227fs)	Pathogenic
2009507	NM_017671.5(FERMT1):c.385+1G>T	Pathogenic
2138331	NM_017671.5(FERMT1):c.1209C>G (p.Tyr403Ter)	Pathogenic
2164966	NM_017671.5(FERMT1):c.894G>A (p.Trp298Ter)	Pathogenic
224165	NM_017671.5(FERMT1):c.1198T>C (p.Ser400Pro)	Pathogenic
224168	NM_017671.5(FERMT1):c.1867_1869del (p.Ile623del)	Pathogenic
224172	NM_017671.4:c.676insC	Pathogenic
224173	NM_017671.5(FERMT1):c.910G>T (p.Glu304Ter)	Pathogenic
224183	NC_000020.11:g.6122304_6124256del	Pathogenic
224184	NM_017671.5(FERMT1):c.850-272_1139+53del	Pathogenic
224185	g.6116239_6120157del	Pathogenic
224186	g.6109607_6112272del	Pathogenic
2419176	NM_017671.5(FERMT1):c.676del (p.Gln226fs)	Pathogenic
2426342	NC_000020.10:g.(?6090925)(6091178_?)del	Pathogenic
2444858	NM_017671.5(FERMT1):c.35G>A (p.Trp12Ter)	Pathogenic
2706697	NM_017671.5(FERMT1):c.1081_1082del (p.Ser361fs)	Pathogenic
2713	NM_017671.5(FERMT1):c.385+2T>C	Pathogenic
2714	NM_017671.5(FERMT1):c.787C>T (p.Gln263Ter)	Pathogenic
2715	NM_017671.5(FERMT1):c.1714_1715insA (p.Val572fs)	Pathogenic
2716	NM_017671.5(FERMT1):c.464del (p.Asn155fs)	Pathogenic
2717	NM_017671.5(FERMT1):c.811C>T (p.Arg271Ter)	Pathogenic

SpliceAI

2149 predictions. Top by Δscore:

Variant	Effect	Δscore
20:6077343:CCAC:C	acceptor_gain	1.0000
20:6077344:CAC:C	acceptor_gain	1.0000
20:6077344:CACC:C	acceptor_gain	1.0000
20:6077345:ACCTG:A	acceptor_loss	1.0000
20:6077346:CCTGG:C	acceptor_loss	1.0000
20:6077347:CTGGA:C	acceptor_loss	1.0000
20:6077348:T:A	acceptor_loss	1.0000
20:6079430:CTTTA:C	donor_loss	1.0000
20:6079431:TTTA:T	donor_loss	1.0000
20:6079432:TTACC:T	donor_loss	1.0000
20:6079433:TACCT:T	donor_loss	1.0000
20:6079435:CCT:C	donor_loss	1.0000
20:6079438:G:A	donor_gain	1.0000
20:6079573:TAAAT:T	acceptor_gain	1.0000
20:6079574:AAAT:A	acceptor_gain	1.0000
20:6079575:AAT:A	acceptor_gain	1.0000
20:6079576:AT:A	acceptor_gain	1.0000
20:6079578:C:CC	acceptor_gain	1.0000
20:6079579:T:C	acceptor_loss	1.0000
20:6084036:TCA:T	donor_loss	1.0000
20:6084037:CA:C	donor_loss	1.0000
20:6084038:A:AT	donor_loss	1.0000
20:6084161:CCAG:C	acceptor_gain	1.0000
20:6084162:CAG:C	acceptor_gain	1.0000
20:6084162:CAGC:C	acceptor_gain	1.0000
20:6084165:C:CC	acceptor_gain	1.0000
20:6085283:TTCTC:T	acceptor_gain	1.0000
20:6085285:CTC:C	acceptor_gain	1.0000
20:6087883:CCTG:C	acceptor_loss	1.0000
20:6087884:C:CC	acceptor_gain	1.0000

AlphaMissense

4485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:6079462:A:G	W612R	0.998
20:6079462:A:T	W612R	0.998
20:6085269:A:G	W464R	0.998
20:6085269:A:T	W464R	0.998
20:6115991:A:G	W69R	0.998
20:6115991:A:T	W69R	0.998
20:6084083:A:G	W559R	0.997
20:6084083:A:T	W559R	0.997
20:6097595:C:G	A296P	0.997
20:6107633:A:G	W250R	0.997
20:6107633:A:T	W250R	0.997
20:6077264:C:T	G648D	0.996
20:6097528:A:G	L318P	0.996
20:6097534:G:T	A316E	0.996
20:6097618:C:G	R288P	0.996
20:6115821:G:C	C125W	0.996
20:6077261:C:T	G649D	0.995
20:6085247:G:T	A471E	0.995
20:6085274:G:T	A462D	0.995
20:6085278:A:C	Y461D	0.995
20:6107562:T:A	K273N	0.995
20:6107562:T:G	K273N	0.995
20:6085257:A:G	C468R	0.994
20:6085262:G:T	A466D	0.994
20:6085267:C:A	W464C	0.994
20:6085267:C:G	W464C	0.994
20:6107563:T:A	K273I	0.994
20:6115951:A:T	V82D	0.994
20:6079542:A:T	V585D	0.993
20:6084043:A:T	V572D	0.993

dbSNP variants (sampled 300 via entrez): RS1000047470 (20:6077335 C>T), RS1000093533 (20:6118307 A>G), RS1000196840 (20:6094548 G>A), RS1000234913 (20:6086929 C>A,G), RS1000247680 (20:6093263 T>C), RS1000347928 (20:6088627 T>C), RS1000390884 (20:6123915 G>T), RS1000401665 (20:6122667 G>C), RS1000498261 (20:6113203 C>A,T), RS1000508526 (20:6116470 T>C), RS1000542275 (20:6116230 A>G), RS1000582625 (20:6075446 C>A), RS1000778646 (20:6100484 A>G), RS1000834606 (20:6122336 C>G), RS1001001116 (20:6078688 A>T)

Disease associations

OMIM: gene MIM:607900 | disease phenotypes: MIM:173650

GenCC curated gene-disease

Disease	Classification	Inheritance
Kindler syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Kindler syndrome	Definitive	AR

Mondo (1): Kindler syndrome (MONDO:0008260)

Orphanet (2): Kindler epidermolysis bullosa (Orphanet:2908), OBSOLETE: Hereditary acrokeratotic poikiloderma of Kindler-Weary (Orphanet:306539)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000230	Gingivitis
HP:0000262	Turricephaly
HP:0000509	Conjunctivitis
HP:0000656	Ectropion
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000704	Periodontitis
HP:0000772	Abnormal rib morphology
HP:0000929	Abnormal skull morphology
HP:0000962	Hyperkeratosis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000987	Atypical scarring of skin
HP:0000992	Cutaneous photosensitivity
HP:0001000	Abnormality of skin pigmentation
HP:0001029	Poikiloderma
HP:0001030	Fragile skin
HP:0001056	Milia
HP:0001371	Flexion contracture
HP:0001581	Recurrent skin infections
HP:0001602	Laryngeal stenosis
HP:0001741	Phimosis
HP:0001807	Ridged nail
HP:0001903	Anemia
HP:0002015	Dysphagia
HP:0002025	Anal stenosis
HP:0002037	Inflammation of the large intestine
HP:0002043	Esophageal stricture
HP:0002583	Colitis

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002361_30	Smooth-surface caries	6.000000e-06
GCST003877_11	Abdominal aortic aneurysm	3.000000e-06
GCST004131_14	Inflammatory bowel disease	1.000000e-08
GCST004132_46	Crohn’s disease	2.000000e-07
GCST008664_17	Lung function (low FEV1 vs high FEV1)	5.000000e-08
GCST009615_19	Triglyceride levels x loop diuretics use interaction	2.000000e-10
GCST009959_22	Retinal detachment or retinal break	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004530	triglyceride measurement
EFO:0010698	retinal break

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536321	Poikiloderma of Kindler (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465350 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
trichostatin A	increases expression, affects expression, affects cotreatment	4
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation, decreases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	decreases expression, increases abundance, affects cotreatment	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5378336	Binding	Binding affinity to His6-tagged KIND1 (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as change in melting temperature by DSF analysis	Discovery of Inhibitory Fragments That Selectively Target Spire2-FMN2 Interaction. — J Med Chem

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	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