FER1L5

Summary

FER1L5 (fer-1 like family member 5, HGNC:19044) is a protein-coding gene on chromosome 2q11.2, encoding Fer-1-like protein 5 (A0AVI2). Plays a crucial role in male fertility, primarily through its involvement in the acrosome reaction of spermatozoa.

Predicted to enable calcium ion binding activity. Predicted to be involved in regulation of neurotransmitter secretion. Predicted to be located in plasma membrane. Predicted to be active in synaptic vesicle membrane.

Source: NCBI Gene 90342 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 304 total
• MANE Select transcript: NM_001293083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19044
Approved symbol	FER1L5
Name	fer-1 like family member 5
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434I0121
Ensembl gene	ENSG00000249715
Ensembl biotype	protein_coding
OMIM	620883
Entrez	90342

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 2 protein_coding

ENST00000457909, ENST00000505256, ENST00000623019, ENST00000624922

RefSeq mRNA: 1 — MANE Select: NM_001293083 NM_001293083

CCDS: CCDS77438

Canonical transcript exons

ENST00000624922 — 53 exons

Exon	Start	End
ENSE00003755000	96647064	96647155
ENSE00003755143	96696052	96696077
ENSE00003755149	96685940	96686117
ENSE00003755253	96668751	96668794
ENSE00003755367	96701955	96702043
ENSE00003755520	96691445	96691612
ENSE00003755643	96692104	96692181
ENSE00003755677	96673077	96673254
ENSE00003755825	96668886	96668968
ENSE00003756178	96654446	96654496
ENSE00003756324	96650180	96650289
ENSE00003756351	96698037	96698156
ENSE00003756402	96700332	96700471
ENSE00003756432	96653640	96653702
ENSE00003756452	96702306	96702401
ENSE00003756519	96697660	96697761
ENSE00003756647	96697526	96697576
ENSE00003756743	96660341	96660371
ENSE00003756918	96663439	96663507
ENSE00003757191	96670119	96670247
ENSE00003757455	96695742	96695904
ENSE00003757564	96690487	96690589
ENSE00003757604	96689644	96689758
ENSE00003757617	96651892	96652020
ENSE00003757620	96685329	96685429
ENSE00003758049	96684327	96684451
ENSE00003758072	96662215	96662267
ENSE00003758177	96699550	96699720
ENSE00003758459	96694360	96694464
ENSE00003758550	96702978	96703077
ENSE00003758661	96647778	96647886
ENSE00003758691	96691190	96691353
ENSE00003758783	96702600	96702741
ENSE00003758963	96704215	96704362
ENSE00003759194	96691825	96691963
ENSE00003759209	96649623	96649677
ENSE00003759296	96669043	96669137
ENSE00003759378	96687816	96687947
ENSE00003759564	96699932	96700080
ENSE00003759621	96686195	96686350
ENSE00003759654	96646401	96646453
ENSE00003759734	96695509	96695661
ENSE00003759789	96703523	96703632
ENSE00003759808	96703153	96703346
ENSE00003759881	96661668	96661791
ENSE00003759934	96698671	96698832
ENSE00003760005	96661325	96661440
ENSE00003760034	96693911	96694072
ENSE00003760076	96689213	96689376
ENSE00003760120	96693506	96693687
ENSE00003760123	96699045	96699136
ENSE00003814043	96704468	96704883
ENSE00003845087	96642764	96642921

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 85.81.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4405 / max 32.9292, expressed in 216 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21477	0.4405	216

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	85.81	gold quality
right testis	UBERON:0004534	78.67	gold quality
left testis	UBERON:0004533	78.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.18	gold quality
left ventricle myocardium	UBERON:0006566	78.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.47	silver quality
testis	UBERON:0000473	75.54	gold quality
pancreatic ductal cell	CL:0002079	73.44	silver quality
body of pancreas	UBERON:0001150	70.02	gold quality
ileal mucosa	UBERON:0000331	69.68	gold quality
tibialis anterior	UBERON:0001385	69.37	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	66.08	gold quality
myocardium	UBERON:0002349	63.89	gold quality
right uterine tube	UBERON:0001302	62.80	gold quality
pancreas	UBERON:0001264	62.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.89	gold quality
deltoid	UBERON:0001476	60.88	silver quality
adenohypophysis	UBERON:0002196	59.15	gold quality
ventricular zone	UBERON:0003053	58.51	gold quality
nucleus accumbens	UBERON:0001882	58.50	gold quality
putamen	UBERON:0001874	58.31	gold quality
caudate nucleus	UBERON:0001873	58.28	gold quality
pituitary gland	UBERON:0000007	57.71	gold quality
colonic epithelium	UBERON:0000397	57.10	gold quality
metanephros cortex	UBERON:0010533	56.89	gold quality
nasal cavity epithelium	UBERON:0005384	56.17	gold quality
metanephros	UBERON:0000081	55.27	gold quality
nasal cavity mucosa	UBERON:0001826	55.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	54.20	gold quality
cerebellar hemisphere	UBERON:0002245	54.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.63

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fer1l5	ENSMUSG00000037432
rattus_norvegicus	Fer1l5	ENSRNOG00000024201
drosophila_melanogaster	mfr	FBGN0266757
caenorhabditis_elegans	fer-1	WBGENE00001414

Paralogs (4): OTOF (ENSG00000115155), DYSF (ENSG00000135636), MYOF (ENSG00000138119), FER1L6 (ENSG00000214814)

Protein

Protein identifiers

Fer-1-like protein 5 — A0AVI2 (reviewed: A0AVI2)

All UniProt accessions (2): A0AVI2, A0A286YFD1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a crucial role in male fertility, primarily through its involvement in the acrosome reaction of spermatozoa. Required for the Ca(2+)-activated fusion of the acrosomal membrane with the plasma membrane during the acrosome. May play a role in skeletal muscle cell development by ensuring effective myoblast fusion and facilitating membrane repair.

Subunit / interactions. Interacts (via second C2 domain) with EHD1 and EHD2. Interacts with STX2.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane.

Cofactor. Binds 3 Ca(2+) ions per C2 domain.

Miscellaneous. Gene prediction based on partial mRNA data.

Similarity. Belongs to the ferlin family.

Isoforms (3)

UniProt ID	Names	Canonical?
A0AVI2-1	1	yes
A0AVI2-2	2
A0AVI2-4	3

RefSeq proteins (1): NP_001280012* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR006614	Peroxin/Ferlin	Domain
IPR012560	Ferlin_A-domain	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
IPR037723	C2D_Ferlin	Domain
IPR037724	C2E_Ferlin	Domain
IPR037725	C2F_Ferlin	Domain
IPR037726	C2A_Ferlin	Domain
IPR055072	Ferlin_DSRM	Domain

Pfam: PF00168, PF08150, PF08165, PF16165, PF22901

UniProt features (30 total): binding site 15, domain 7, topological domain 2, splice variant 2, sequence variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0AVI2-F1	74.71	0.11

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 (15): 1502; 1502; 1508; 1557; 1557; 1558; 1559; 1559; 1559; 1562; 1565; 1565 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_WOUND_HEALING, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_SPERM_EGG_RECOGNITION, GOBP_REGULATION_OF_NEUROTRANSMITTER_TRANSPORT, GOBP_SECRETION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SIGNAL_RELEASE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (5): plasma membrane repair (GO:0001778), membrane fusion involved in acrosome reaction (GO:0002078), binding of sperm to zona pellucida (GO:0007339), myoblast fusion (GO:0007520), regulation of neurotransmitter secretion (GO:0046928)

GO Molecular Function (2): calcium ion binding (GO:0005509), metal ion binding (GO:0046872)

GO Cellular Component (4): plasma membrane (GO:0005886), cytoplasmic vesicle membrane (GO:0030659), synaptic vesicle membrane (GO:0030672), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane organization	1
wound healing	1
acrosome reaction	1
cellular process involved in reproduction in multicellular organism	1
membrane fusion	1
sperm-egg recognition	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
neurotransmitter secretion	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
metal ion binding	1
cation binding	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
synaptic vesicle	1
exocytic vesicle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FER1L5	EHD2	Q9NZN4	737
FER1L5	EHD3	Q9NZN3	683
FER1L5	EHD1	Q9H4M9	539
FER1L5	FAHD2B	Q6P2I3	512
FER1L5	FAM178B	Q8IXR5	506
FER1L5	ANKRD39	Q53RE8	505
FER1L5	TMEM253	P0C7T8	448
FER1L5	LMAN2L	Q9H0V9	445
FER1L5	CNNM4	Q6P4Q7	435
FER1L5	ITPRIPL1	Q6GPH6	416
FER1L5	ARHGAP26	Q9UNA1	404
FER1L5	EPS15	P42566	403
FER1L5	EMG1	Q92979	402
FER1L5	PKDREJ	Q9NTG1	401
FER1L5	ANKRD36	A6QL64	370

IntAct

3 interactions, top by confidence:

A	B	Type	Score
FER1L5	H1-4	psi-mi:“MI:0915”(physical association)	0.400
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): HIST1H1E (Proximity Label-MS), FER1L5 (Proximity Label-MS), FER1L5 (Affinity Capture-RNA), FER1L5 (Proximity Label-MS), FER1L5 (Proximity Label-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: A0AVI2, A3KGK3, A6QQP7, B3DLH6, O75923, P0DM40, Q69ZN7, Q8LFN9, Q9C6B7, Q9ESD7, Q9NZM1, Q9Z268, A0JJX5, B2RUP2, C9J798, O43374, O95294, P48231, Q2WGJ9, Q54E35, Q5SPC5, Q8L706, Q8L7A4, Q8W4D4, Q9ERC5, Q9ESF1, Q9FVJ3, Q9HC10, Q9R189, Q9UT00, A1ZBD6, B6ETT4, D4ABL6, E9PV86, K8FE10, O00445, O35681, P05128, P05129, P05130

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	263
Likely benign	27
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

9298 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96647772:CCCCA:C	acceptor_loss	1.0000
2:96647773:CCCA:C	acceptor_loss	1.0000
2:96647775:CAG:C	acceptor_loss	1.0000
2:96647776:A:AG	acceptor_gain	1.0000
2:96647776:A:T	acceptor_loss	1.0000
2:96647777:G:GG	acceptor_gain	1.0000
2:96647777:G:GT	acceptor_loss	1.0000
2:96647884:GAT:G	donor_gain	1.0000
2:96647887:G:GG	donor_gain	1.0000
2:96647902:G:GT	donor_gain	1.0000
2:96649621:A:AG	acceptor_gain	1.0000
2:96649622:G:GA	acceptor_gain	1.0000
2:96649622:GT:G	acceptor_gain	1.0000
2:96649622:GTGT:G	acceptor_gain	1.0000
2:96649622:GTGTA:G	acceptor_gain	1.0000
2:96649673:GACAG:G	donor_gain	1.0000
2:96649674:ACAGG:A	donor_loss	1.0000
2:96649677:GGT:G	donor_loss	1.0000
2:96649679:T:G	donor_loss	1.0000
2:96650179:GGA:G	acceptor_gain	1.0000
2:96651887:CTTA:C	acceptor_loss	1.0000
2:96651888:TTA:T	acceptor_loss	1.0000
2:96651890:A:AG	acceptor_gain	1.0000
2:96651890:A:AT	acceptor_loss	1.0000
2:96651891:G:GG	acceptor_gain	1.0000
2:96651891:GGTTC:G	acceptor_gain	1.0000
2:96651994:A:G	donor_gain	1.0000
2:96651998:G:T	donor_gain	1.0000
2:96654497:G:GG	donor_gain	1.0000
2:96661793:T:G	donor_gain	1.0000

AlphaMissense

13633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96703305:T:A	W1884R	0.997
2:96703305:T:C	W1884R	0.997
2:96699948:T:A	W1600R	0.995
2:96699948:T:C	W1600R	0.995
2:96661397:T:C	L284P	0.994
2:96663478:T:A	W371R	0.993
2:96663478:T:C	W371R	0.993
2:96670162:G:C	R469P	0.993
2:96698152:T:C	F1451S	0.993
2:96698678:T:C	F1455S	0.993
2:96698780:G:C	R1489P	0.993
2:96702317:G:C	R1724P	0.993
2:96698156:G:C	K1452N	0.992
2:96698156:G:T	K1452N	0.992
2:96703542:T:C	L1904P	0.992
2:96701970:T:A	W1696R	0.991
2:96701970:T:C	W1696R	0.991
2:96703302:T:A	W1883R	0.991
2:96703302:T:C	W1883R	0.991
2:96703307:G:C	W1884C	0.991
2:96703307:G:T	W1884C	0.991
2:96661345:T:A	W267R	0.990
2:96661345:T:C	W267R	0.990
2:96673170:A:C	S529R	0.990
2:96673172:C:A	S529R	0.990
2:96673172:C:G	S529R	0.990
2:96699591:T:C	L1551P	0.990
2:96689336:T:A	W829R	0.989
2:96689336:T:C	W829R	0.989
2:96699950:G:C	W1600C	0.989

dbSNP variants (sampled 300 via entrez): RS1000011491 (2:96653092 C>A), RS1000053354 (2:96696797 A>C,G), RS1000075546 (2:96703997 G>A), RS1000101200 (2:96670501 G>A), RS1000102953 (2:96658190 G>A,T), RS1000147969 (2:96654948 C>A), RS1000183365 (2:96681881 G>A), RS1000223944 (2:96705098 G>A), RS1000253212 (2:96652872 G>A), RS1000311469 (2:96646297 C>A,G,T), RS1000364834 (2:96646136 C>T), RS1000422617 (2:96674546 T>A), RS1000426136 (2:96687533 C>T), RS1000446542 (2:96652923 C>A), RS1000452214 (2:96674155 T>C)

Disease associations

OMIM: gene MIM:620883 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001241_9	Bipolar disorder	2.000000e-06
GCST003962_1	Bipolar disorder	3.000000e-10
GCST006166_50	Diastolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-10
GCST006166_84	Diastolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-11
GCST006190_24	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-11
GCST006190_31	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-11
GCST006193_15	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-12
GCST006193_55	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-13
GCST006865_6	Bipolar disorder	3.000000e-06
GCST007094_109	Diastolic blood pressure	1.000000e-07
GCST008103_13	Bipolar disorder	4.000000e-09
GCST90020028_63	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aminomethylphosphonic acid (AMPA)	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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