FRMD1

Summary

FRMD1 (FERM domain containing 1, HGNC:21240) is a protein-coding gene on chromosome 6q27, encoding FERM domain-containing protein 1 (Q8N878).

Predicted to be involved in positive regulation of hippo signaling. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasmic side of apical plasma membrane.

Source: NCBI Gene 79981 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_024919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21240
Approved symbol	FRMD1
Name	FERM domain containing 1
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00181, DKFZp434O0117, FLJ40260, FLJ22615, bA164L23.1
Ensembl gene	ENSG00000153303
Ensembl biotype	protein_coding
Entrez	79981

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000283309, ENST00000336070, ENST00000358587, ENST00000432403, ENST00000440994, ENST00000468647, ENST00000506415, ENST00000509157, ENST00000511714, ENST00000644440, ENST00000646385

RefSeq mRNA: 3 — MANE Select: NM_024919 NM_001122841, NM_001394681, NM_024919

CCDS: CCDS47518, CCDS5306, CCDS94036

Canonical transcript exons

ENST00000283309 — 11 exons

Exon	Start	End
ENSE00001355851	168078882	168079212
ENSE00002027656	168053095	168057339
ENSE00003504311	168062894	168062959
ENSE00003539387	168067367	168067446
ENSE00003546222	168064871	168065057
ENSE00003553321	168059124	168059188
ENSE00003638162	168075245	168075335
ENSE00003662641	168060761	168061057
ENSE00003681330	168063601	168063756
ENSE00003682212	168061807	168061981
ENSE00003788885	168066755	168066831

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 88.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3054 / max 107.6608, expressed in 65 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76730	0.1147	30
76732	0.0652	17
76731	0.0551	3
76733	0.0321	11
76725	0.0221	3
76727	0.0083	3
76726	0.0077	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	88.17	gold quality
sural nerve	UBERON:0015488	87.74	gold quality
body of stomach	UBERON:0001161	78.51	gold quality
tibial nerve	UBERON:0001323	77.88	gold quality
transverse colon	UBERON:0001157	77.39	gold quality
rectum	UBERON:0001052	76.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.48	gold quality
stomach	UBERON:0000945	74.23	gold quality
right testis	UBERON:0004534	73.05	gold quality
left testis	UBERON:0004533	72.97	gold quality
fundus of stomach	UBERON:0001160	72.80	gold quality
metanephric glomerulus	UBERON:0004736	72.23	silver quality
renal glomerulus	UBERON:0000074	72.11	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.78	gold quality
testis	UBERON:0000473	70.37	gold quality
nephron tubule	UBERON:0001231	70.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.82	gold quality
trigeminal ganglion	UBERON:0001675	69.70	silver quality
pharyngeal mucosa	UBERON:0000355	69.50	gold quality
colonic mucosa	UBERON:0000317	69.43	gold quality
nipple	UBERON:0002030	69.43	gold quality
superior surface of tongue	UBERON:0007371	69.39	gold quality
cardia of stomach	UBERON:0001162	69.33	gold quality
vena cava	UBERON:0004087	69.25	gold quality
saphenous vein	UBERON:0007318	69.12	gold quality
subthalamic nucleus	UBERON:0001906	68.94	gold quality
inferior vagus X ganglion	UBERON:0005363	68.85	gold quality
adult mammalian kidney	UBERON:0000082	68.82	gold quality
pericardium	UBERON:0002407	68.78	gold quality
body of tongue	UBERON:0011876	68.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting FRMD1, 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-1193	100.00	65.93	529
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-943	97.81	64.42	694
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-2861	95.24	65.47	1056

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	FRMD1	ENSDARG00000078741
danio_rerio	si:ch73-205h11.1	ENSDARG00000096757
drosophila_melanogaster	ex	FBGN0004583
caenorhabditis_elegans		WBGENE00001493

Protein

Protein identifiers

FERM domain-containing protein 1 — Q8N878 (reviewed: Q8N878)

All UniProt accessions (7): Q8N878, A0A2R8Y4L9, A0A2R8Y579, A0A2R8Y6M2, A0A2R8Y7X7, D6RB43, H0Y9A3

UniProt curated annotations — full annotation on UniProt →

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N878-1	1	yes
Q8N878-2	2

RefSeq proteins (3): NP_001116313, NP_001381610, NP_079195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR047145	FRMD6-like	Family

Pfam: PF00373, PF09379

UniProt features (10 total): region of interest 3, compositionally biased region 2, sequence variant 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N878-F1	66.72	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GOBP_HIPPO_SIGNALING, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, chr6q27, GOCC_CELL_CELL_JUNCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_ANCHORING_JUNCTION, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_REGULATION_OF_HIPPO_SIGNALING, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ATF2_UP.V1_UP, PTEN_DN.V2_DN, IL15_UP.V1_DN, KRAS.600.LUNG.BREAST_UP.V1_UP, KRAS.LUNG_UP.V1_UP

GO Biological Process (1): positive regulation of hippo signaling (GO:0035332)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasmic side of apical plasma membrane (GO:0098592), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
binding	1
cytoplasmic side of plasma membrane	1
apical plasma membrane	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FRMD1	KIF25	Q9UIL4	627
FRMD1	WWC3	Q9ULE0	589
FRMD1	DYNLT2	Q8IZS6	574
FRMD1	DACT2	Q5SW24	566
FRMD1	WDR27	A2RRH5	547
FRMD1	WWC2	Q6AWC2	525
FRMD1	KRTAP2-1	Q9BYU5	506
FRMD1	SMOC2	Q9H3U7	501
FRMD1	PHF10	Q8WUB8	479
FRMD1	MAST3	O60307	475
FRMD1	KRTAP2-2	Q9BYT5	468
FRMD1	CMTM8	Q8IZV2	466
FRMD1	KASH5	Q8N6L0	460
FRMD1	SPRR4	Q96PI1	445
FRMD1	BKGD	Q9H0W9	442

IntAct

10 interactions, top by confidence:

A	B	Type	Score
RAB2A	FRMD1	psi-mi:“MI:0915”(physical association)	0.560
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
PIN4	FRMD1	psi-mi:“MI:0915”(physical association)	0.490
ORF4	DNM1L	psi-mi:“MI:0914”(association)	0.350
FRMD1	TRIM37	psi-mi:“MI:0914”(association)	0.350
FRMD1	RAB2A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (91): MUC7 (Affinity Capture-MS), BPIFA2 (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MPO (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), SCEL (Affinity Capture-MS), SPRR3 (Affinity Capture-MS), PIGR (Affinity Capture-MS), SKAP2 (Affinity Capture-MS), CRNN (Affinity Capture-MS), AMY1C (Affinity Capture-MS), GBP6 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), CST2 (Affinity Capture-MS), A2ML1 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB4, A2APT9, O54824, P49796, Q0V8R5, Q14005, Q32LQ1, Q3B7M3, Q3TYG6, Q494U1, Q4FZU8, Q4V7B1, Q5BJM5, Q5JV73, Q5RA50, Q5SYB0, Q5T7N3, Q68FE6, Q6P1H6, Q6P9J5, Q6PCP7, Q6PG95, Q6ZPF3, Q6ZUX3, Q7TNY7, Q7TP65, Q80TI1, Q80UZ0, Q80XI1, Q80YE4, Q86V42, Q86XL3, Q8BLK9, Q8C886, Q8IVF5, Q8K124, Q8K3I4, Q8K451, Q8N5H7, Q8N878

Diamond homologs: Q8C0V9, Q8N878, Q8VII0, Q96NE9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	17
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

2337 predictions. Top by Δscore:

Variant	Effect	Δscore
6:168057340:C:CA	acceptor_loss	1.0000
6:168057340:C:CC	acceptor_gain	1.0000
6:168061056:CT:C	acceptor_gain	1.0000
6:168061815:T:TA	donor_gain	1.0000
6:168061818:T:TA	donor_gain	1.0000
6:168061819:C:CA	donor_gain	1.0000
6:168061831:G:C	donor_gain	1.0000
6:168063529:AG:A	donor_gain	1.0000
6:168063530:G:C	donor_gain	1.0000
6:168063550:C:A	donor_gain	1.0000
6:168063588:C:CA	donor_gain	1.0000
6:168063632:T:TA	donor_gain	1.0000
6:168063650:T:TA	donor_gain	1.0000
6:168063753:TGAT:T	acceptor_gain	1.0000
6:168063755:AT:A	acceptor_gain	1.0000
6:168063755:ATC:A	acceptor_loss	1.0000
6:168063757:C:CC	acceptor_gain	1.0000
6:168064870:CCCA:C	donor_gain	1.0000
6:168064906:T:TA	donor_gain	1.0000
6:168064907:C:A	donor_gain	1.0000
6:168066750:GTTA:G	donor_loss	1.0000
6:168066752:TACCT:T	donor_loss	1.0000
6:168066753:ACC:A	donor_loss	1.0000
6:168066756:TTATG:T	donor_gain	1.0000
6:168066758:ATGAC:A	donor_gain	1.0000
6:168066830:CC:C	acceptor_gain	1.0000
6:168066831:CC:C	acceptor_gain	1.0000
6:168066931:G:C	donor_gain	1.0000
6:168067360:CACTT:C	donor_loss	1.0000
6:168067361:ACTTA:A	donor_loss	1.0000

AlphaMissense

3605 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:168063658:G:C	F249L	0.990
6:168063658:G:T	F249L	0.990
6:168063660:A:G	F249L	0.990
6:168065035:A:C	Y162D	0.990
6:168064898:G:C	F207L	0.987
6:168064898:G:T	F207L	0.987
6:168064900:A:G	F207L	0.987
6:168065018:C:A	K167N	0.985
6:168065018:C:G	K167N	0.985
6:168067410:A:T	L114H	0.983
6:168067430:A:C	F107L	0.980
6:168067430:A:T	F107L	0.980
6:168067432:A:G	F107L	0.980
6:168067387:A:G	W122R	0.979
6:168067387:A:T	W122R	0.979
6:168063648:C:G	A253P	0.978
6:168075265:A:G	F95S	0.978
6:168064881:A:G	F213S	0.977
6:168075264:A:C	F95L	0.977
6:168075264:A:T	F95L	0.977
6:168075266:A:G	F95L	0.977
6:168075259:A:T	L97H	0.975
6:168075313:A:T	L79H	0.975
6:168067385:C:A	W122C	0.974
6:168067385:C:G	W122C	0.974
6:168075313:A:G	L79P	0.974
6:168075322:C:T	G76D	0.974
6:168064878:G:T	P214Q	0.973
6:168063659:A:G	F249S	0.972
6:168064962:G:T	A186D	0.971

dbSNP variants (sampled 300 via entrez): RS1000002206 (6:168091180 T>C), RS1000025484 (6:168069580 C>A), RS1000095756 (6:168074801 G>C), RS1000137048 (6:168093731 A>G), RS1000295096 (6:168059944 A>C,G), RS1000346801 (6:168060536 C>G,T), RS1000534435 (6:168077139 A>C), RS1000550879 (6:168074992 T>C,G), RS1000571142 (6:168066169 C>A,T), RS1000577975 (6:168071105 G>C), RS1000627461 (6:168061383 G>A,C), RS1000737496 (6:168092743 T>C), RS1000802021 (6:168091774 C>T), RS1000810380 (6:168066669 A>C,G), RS1000817767 (6:168082353 C>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614065

GenCC curated gene-disease

Mondo (1): distal myopathy with posterior leg and anterior hand involvement (MONDO:0013550)

Orphanet (1): FLNC-related handgrip and calf weakness-distal myopathy (Orphanet:63273)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001535_4	Immune reponse to smallpox (secreted IL-2)	3.000000e-07
GCST004068_14	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	6.000000e-06
GCST009391_547	Metabolite levels	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0010496	hippuric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
ferrous chloride	increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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