FER1L6

Summary

FER1L6 (fer-1 like family member 6, HGNC:28065) is a protein-coding gene on chromosome 8q24.13, encoding Fer-1-like protein 6 (Q2WGJ9). Calcium/phospholipid-binding protein which is essential for proper development of skeletal and cardiac muscle.

Predicted to enable metal ion binding activity. Predicted to be involved in positive regulation of gene expression. Predicted to act upstream of or within response to bacterium. Predicted to be located in membrane.

Source: NCBI Gene 654463 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 287 total
• MANE Select transcript: NM_001039112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28065
Approved symbol	FER1L6
Name	fer-1 like family member 6
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	C8ORFK23
Ensembl gene	ENSG00000214814
Ensembl biotype	protein_coding
OMIM	620884
Entrez	654463

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000522917

RefSeq mRNA: 1 — MANE Select: NM_001039112 NM_001039112

CCDS: CCDS43767

Canonical transcript exons

ENST00000522917 — 41 exons

Exon	Start	End
ENSE00001536004	124119607	124120061
ENSE00001536005	124118844	124118944
ENSE00001536009	124103146	124103309
ENSE00001536013	124101097	124101338
ENSE00001536017	124097785	124097883
ENSE00001536019	124097271	124097359
ENSE00001536021	124094896	124095038
ENSE00001536023	124091423	124091583
ENSE00001536025	124082288	124082458
ENSE00001536027	124076198	124076325
ENSE00001536028	124071506	124071631
ENSE00001536031	124070467	124070598
ENSE00001536034	124069360	124069475
ENSE00001536037	124067767	124067806
ENSE00001536039	124066428	124066550
ENSE00001536042	124064347	124064573
ENSE00001536043	124061852	124062032
ENSE00001536050	124060548	124060709
ENSE00001536054	124060180	124060290
ENSE00001536058	124049607	124049756
ENSE00001536063	124045767	124045901
ENSE00001536066	124039882	124040006
ENSE00001536069	124035277	124035454
ENSE00001536072	124023444	124023596
ENSE00001536074	124021550	124021669
ENSE00001536078	124017628	124017718
ENSE00001536079	124013431	124013531
ENSE00001536083	124010594	124010714
ENSE00001536087	124003167	124003347
ENSE00001536094	123986068	123986176
ENSE00001536099	123980465	123980811
ENSE00001536107	123977417	123977609
ENSE00001536109	123975898	123976084
ENSE00001536110	123975150	123975306
ENSE00001536115	123973434	123973512
ENSE00001536116	123970035	123970097
ENSE00001536117	123966159	123966290
ENSE00001536121	123966007	123966061
ENSE00001536122	123963278	123963398
ENSE00002120426	123851987	123852185
ENSE00002139439	123955992	123956074

Expression profiles

Bgee: expression breadth broad, 65 present calls, max score 77.91.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	77.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.17	silver quality
duodenum	UBERON:0002114	70.11	gold quality
stomach	UBERON:0000945	64.47	gold quality
mucosa of stomach	UBERON:0001199	62.80	gold quality
body of stomach	UBERON:0001161	62.65	gold quality
mucosa of transverse colon	UBERON:0004991	58.74	gold quality
small intestine	UBERON:0002108	58.29	gold quality
transverse colon	UBERON:0001157	57.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	57.11	gold quality
colonic epithelium	UBERON:0000397	56.45	silver quality
adult mammalian kidney	UBERON:0000082	55.13	gold quality
kidney	UBERON:0002113	54.60	gold quality
stromal cell of endometrium	CL:0002255	54.35	gold quality
testis	UBERON:0000473	54.13	gold quality
left testis	UBERON:0004533	53.41	gold quality
fundus of stomach	UBERON:0001160	53.35	gold quality
right testis	UBERON:0004534	52.88	gold quality
islet of Langerhans	UBERON:0000006	52.18	gold quality
intestine	UBERON:0000160	51.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.42	gold quality
vermiform appendix	UBERON:0001154	50.31	gold quality
right uterine tube	UBERON:0001302	49.84	gold quality
cortex of kidney	UBERON:0001225	49.77	gold quality
colon	UBERON:0001155	48.33	gold quality
muscle tissue	UBERON:0002385	48.29	gold quality
skeletal muscle tissue	UBERON:0001134	48.24	gold quality
smooth muscle tissue	UBERON:0001135	46.32	gold quality
thyroid gland	UBERON:0002046	45.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting FER1L6, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fer1l6	ENSDARG00000019316
mus_musculus	Fer1l6	ENSMUSG00000037106
rattus_norvegicus	Fer1l6	ENSRNOG00000025300
drosophila_melanogaster	mfr	FBGN0266757

Paralogs (4): OTOF (ENSG00000115155), DYSF (ENSG00000135636), MYOF (ENSG00000138119), FER1L5 (ENSG00000249715)

Protein

Protein identifiers

Fer-1-like protein 6 — Q2WGJ9 (reviewed: Q2WGJ9)

All UniProt accessions (1): Q2WGJ9

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/phospholipid-binding protein which is essential for proper development of skeletal and cardiac muscle.

Subunit / interactions. Interacts with STX4 and VCL.

Subcellular location. Cell membrane. Cytoplasm. Perinuclear region. Golgi apparatus. trans-Golgi network. Recycling endosome.

Domain organisation. The C2 domain associates with lipid membranes in a calcium-dependent manner.

Similarity. Belongs to the ferlin family.

RefSeq proteins (1): NP_001034201* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR012561	Ferlin_B-domain	Domain
IPR012968	FerIin_dom	Domain
IPR032362	Ferlin_C	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037720	C2B_Ferlin	Domain
IPR037721	Ferlin	Family
IPR037722	C2C_Ferlin	Domain
IPR037723	C2D_Ferlin	Domain
IPR037724	C2E_Ferlin	Domain
IPR037725	C2F_Ferlin	Domain
IPR055072	Ferlin_DSRM	Domain

Pfam: PF00168, PF08150, PF08151, PF16165, PF22901

UniProt features (36 total): binding site 12, compositionally biased region 7, domain 6, region of interest 5, topological domain 2, chain 1, transmembrane region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2WGJ9-F1	76.78	0.39

Functional residue map

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

Ligand- & substrate-binding residues (12): 842; 848; 904; 906; 1372; 1372; 1378; 1427; 1427; 1429; 1429; 1435

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOCC_TRANS_GOLGI_NETWORK, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOCC_RECYCLING_ENDOSOME, GOCC_ORGANELLE_SUBCOMPARTMENT, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOBP_RESPONSE_TO_BACTERIUM, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, GOMF_CALCIUM_DEPENDENT_PHOSPHOLIPID_BINDING, WIERENGA_PML_INTERACTOME, chr8q24, MIR6515_3P

GO Biological Process (4): skeletal muscle tissue development (GO:0007519), response to bacterium (GO:0009617), positive regulation of gene expression (GO:0010628), cardiac muscle tissue development (GO:0048738)

GO Molecular Function (2): calcium-dependent phospholipid binding (GO:0005544), metal ion binding (GO:0046872)

GO Cellular Component (5): trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
striated muscle tissue development	2
cellular anatomical structure	2
skeletal muscle organ development	1
response to other organism	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
heart development	1
phospholipid binding	1
cation binding	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
cytoplasm	1
endosome	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FER1L6	MEIG1	Q5JSS6	580
FER1L6	EMG1	Q92979	474
FER1L6	PLEKHG7	Q6ZR37	462
FER1L6	FAM186A	A6NE01	448
FER1L6	IMMP2L	Q96T52	425
FER1L6	GOLGA6L2	Q8N9W4	419
FER1L6	OR2A14	Q96R47	393
FER1L6	SYCE1	Q8N0S2	369
FER1L6	EHD2	Q9NZN4	360
FER1L6	CLRN3	Q8NCR9	356
FER1L6	CCSAP	Q6IQ19	352
FER1L6	SRRM4	A7MD48	348
FER1L6	STOX1	Q6ZVD7	348
FER1L6	GLRX5	Q86SX6	348
FER1L6	CLCA2	Q9UQC9	348
FER1L6	ADGRV1	Q8WXG9	348

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FER1L6	CKMT2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (10): FER1L6 (Proximity Label-MS), FER1L6 (Proximity Label-MS), FER1L6 (Reconstituted Complex), FER1L6 (Cross-Linking-MS (XL-MS)), FER1L6 (Cross-Linking-MS (XL-MS)), FER1L6 (Cross-Linking-MS (XL-MS)), FER1L6 (Cross-Linking-MS (XL-MS)), HDAC2 (Cross-Linking-MS (XL-MS)), PXDNL (Cross-Linking-MS (XL-MS)), MIF (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0AVI2, A0FGR9, A3KGK3, A6NCM1, A6QQP7, B0DOB4, B3DLH6, B7FF09, B7ZC32, D3ZGS3, F1S5L4, O00329, O35904, O70145, O75923, P0DM40, P32019, P58069, P97564, Q0VA04, Q15283, Q17I16, Q1LXZ7, Q2WGJ9, Q32PH0, Q5DTI8, Q5GJ77, Q5RE88, Q5T0N1, Q5XIZ9, Q61586, Q62240, Q63713, Q69ZN7, Q6DCF6, Q6P5U7, Q6PA97, Q86VS3, Q86YR7, Q8BWR4

Diamond homologs: A0JJX5, A1CQG2, A1ZBD6, A2QQ28, A3KGK3, A4IFJ5, A6QQP7, A8KBH6, B1WAZ6, B8N7E5, G0S9J5, O14065, O14795, O43581, O75131, O75923, O94812, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P0C869, P0C871, P10102, P10829, P13677, P17252, P20444, P21521, P27715, P29101, P41823, P41885, P46097, P46935, P49147, P63318

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	231
Likely benign	19
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

6395 predictions. Top by Δscore:

Variant	Effect	Δscore
8:123963277:GATA:G	acceptor_gain	1.0000
8:123966261:G:GT	donor_gain	1.0000
8:123966286:ATGAA:A	donor_gain	1.0000
8:123966287:TGAA:T	donor_gain	1.0000
8:123966288:G:GT	donor_gain	1.0000
8:123966288:GAA:G	donor_gain	1.0000
8:123966290:AG:A	donor_loss	1.0000
8:123966291:G:GG	donor_gain	1.0000
8:123966291:GT:G	donor_loss	1.0000
8:123966292:T:G	donor_loss	1.0000
8:123970033:A:AG	acceptor_gain	1.0000
8:123970034:G:GG	acceptor_gain	1.0000
8:123973428:CCTCA:C	acceptor_loss	1.0000
8:123973429:CTCA:C	acceptor_loss	1.0000
8:123973430:TCA:T	acceptor_loss	1.0000
8:123973431:CAG:C	acceptor_loss	1.0000
8:123973432:A:AT	acceptor_loss	1.0000
8:123973509:CCTGG:C	donor_loss	1.0000
8:123973513:G:GC	donor_loss	1.0000
8:123973514:T:TC	donor_loss	1.0000
8:123975302:GAAAA:G	donor_gain	1.0000
8:123975307:G:GG	donor_gain	1.0000
8:123975390:G:A	acceptor_gain	1.0000
8:123976031:GAC:G	donor_gain	1.0000
8:123976032:ACA:A	donor_gain	1.0000
8:123976035:G:GG	donor_gain	1.0000
8:123977415:AG:A	acceptor_gain	1.0000
8:123977416:GG:G	acceptor_gain	1.0000
8:123977416:GGGGC:G	acceptor_gain	1.0000
8:123977606:AAAGG:A	donor_loss	1.0000

AlphaMissense

12337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:124101176:T:A	W1655R	1.000
8:124101176:T:C	W1655R	1.000
8:124118856:G:C	A1768P	1.000
8:123977456:T:A	W304R	0.999
8:123977456:T:C	W304R	0.999
8:124045794:T:A	W873R	0.999
8:124045794:T:C	W873R	0.999
8:124066512:T:A	W1214R	0.999
8:124066512:T:C	W1214R	0.999
8:124097793:T:C	L1598S	0.999
8:124097812:C:A	N1604K	0.999
8:124097812:C:G	N1604K	0.999
8:124101180:G:C	R1656P	0.999
8:124101294:T:C	L1694P	0.999
8:124101302:T:A	W1697R	0.999
8:124101302:T:C	W1697R	0.999
8:124103251:T:A	I1744K	0.999
8:124103277:T:A	W1753R	0.999
8:124103277:T:C	W1753R	0.999
8:124103280:T:A	W1754R	0.999
8:124103280:T:C	W1754R	0.999
8:124118851:T:A	V1766D	0.999
8:124118857:C:A	A1768D	0.999
8:124118863:T:C	F1770S	0.999
8:124118869:T:C	L1772P	0.999
8:124039969:C:A	A851D	0.998
8:124045796:G:C	W873C	0.998
8:124045796:G:T	W873C	0.998
8:124049731:T:C	L950P	0.998
8:124049749:T:C	L956P	0.998

dbSNP variants (sampled 300 via entrez): RS1000014015 (8:124055176 C>A,T), RS1000025475 (8:123870874 T>C), RS1000027589 (8:123918943 C>A), RS1000036697 (8:124001687 G>C), RS1000044054 (8:124006360 G>T), RS1000058137 (8:123871149 A>C), RS1000062850 (8:124017879 T>C,G), RS1000065553 (8:124062335 T>C), RS1000070603 (8:123994989 T>C), RS1000071451 (8:124106601 A>T), RS1000084676 (8:124044100 T>C), RS1000090096 (8:124002009 G>A), RS1000093575 (8:124017608 T>C), RS1000102057 (8:124106447 G>A), RS1000116970 (8:123974949 A>G)

Disease associations

OMIM: gene MIM:620884 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): congenital portosystemic shunt (MONDO:0018811)

Orphanet (1): Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
sodium arsenite	increases expression	1
(+)-JQ1 compound	decreases expression	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Cadmium	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phthalic Acids	decreases methylation	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	affects methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06041906	Not specified	ENROLLING_BY_INVITATION	International Registry of Congenital Portosystemic Shunt (IRCPSS)
NCT07314814	Not specified	NOT_YET_RECRUITING	Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension