FHAD1

Summary

FHAD1 (forkhead associated phosphopeptide binding domain 1, HGNC:29408) is a protein-coding gene on chromosome 1p36.21, encoding Forkhead-associated domain-containing protein 1 (B1AJZ9). Regulator of sperm motility and spermatocyte meiosis.

Predicted to act upstream of or within apoptotic process and spermatogenesis. Located in sperm flagellum.

Source: NCBI Gene 114827 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 236 total — 1 likely-pathogenic
• MANE Select transcript: NM_001391957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29408
Approved symbol	FHAD1
Name	forkhead associated phosphopeptide binding domain 1
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1937
Ensembl gene	ENSG00000142621
Ensembl biotype	protein_coding
OMIM	620889
Entrez	114827

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 13 protein_coding, 8 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000314668, ENST00000358897, ENST00000375995, ENST00000375996, ENST00000375997, ENST00000375998, ENST00000433640, ENST00000444385, ENST00000459961, ENST00000462113, ENST00000471347, ENST00000472086, ENST00000472131, ENST00000472449, ENST00000477846, ENST00000481324, ENST00000483120, ENST00000483694, ENST00000495195, ENST00000524761, ENST00000529606, ENST00000532408, ENST00000683790, ENST00000688493, ENST00000940095, ENST00000968213

RefSeq mRNA: 2 — MANE Select: NM_001391957 NM_001391957, NM_052929

CCDS: CCDS90866

Canonical transcript exons

ENST00000688493 — 34 exons

Exon	Start	End
ENSE00001635046	15374502	15374631
ENSE00001663227	15301205	15301441
ENSE00001684628	15296684	15296793
ENSE00001763069	15289399	15289666
ENSE00001769396	15272323	15272529
ENSE00003461440	15349042	15349149
ENSE00003461727	15391210	15391263
ENSE00003462723	15345416	15345523
ENSE00003484579	15329346	15329541
ENSE00003490890	15308613	15308736
ENSE00003509575	15362642	15362726
ENSE00003522950	15358110	15358283
ENSE00003527950	15375603	15375730
ENSE00003540539	15365827	15365933
ENSE00003551683	15382028	15382193
ENSE00003556144	15369370	15369502
ENSE00003561984	15360478	15360703
ENSE00003602992	15367463	15367622
ENSE00003614203	15313057	15313187
ENSE00003647179	15327059	15327142
ENSE00003652902	15381231	15381451
ENSE00003654485	15317824	15317928
ENSE00003664267	15380701	15380796
ENSE00003666163	15324452	15324559
ENSE00003674002	15251771	15251877
ENSE00003675424	15316378	15316467
ENSE00003684578	15345083	15345190
ENSE00003686353	15352877	15352984
ENSE00003788031	15328277	15328429
ENSE00003916780	15341736	15341888
ENSE00003917332	15388051	15388131
ENSE00003918246	15397297	15398328
ENSE00003921997	15339481	15339551
ENSE00003925918	15247223	15247395

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 96.57.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0957 / max 53.0858, expressed in 359 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
821	0.3368	149
822	0.1774	86
829	0.1583	57
831	0.1376	72
837	0.0728	31
836	0.0464	15
838	0.0414	19
830	0.0401	10
832	0.0329	13
834	0.0303	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.57	gold quality
bronchial epithelial cell	CL:0002328	94.91	gold quality
bronchus	UBERON:0002185	93.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.70	gold quality
left testis	UBERON:0004533	89.62	gold quality
right testis	UBERON:0004534	89.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.84	gold quality
testis	UBERON:0000473	86.58	gold quality
oviduct epithelium	UBERON:0004804	82.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.48	gold quality
buccal mucosa cell	CL:0002336	81.24	gold quality
fallopian tube	UBERON:0003889	80.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.49	gold quality
endothelial cell	CL:0000115	71.66	gold quality
right lung	UBERON:0002167	69.58	gold quality
endocervix	UBERON:0000458	68.72	gold quality
nasal cavity mucosa	UBERON:0001826	68.19	gold quality
upper lobe of left lung	UBERON:0008952	67.91	gold quality
prefrontal cortex	UBERON:0000451	67.87	gold quality
right adrenal gland cortex	UBERON:0035827	67.65	gold quality
sural nerve	UBERON:0015488	67.46	gold quality
upper lobe of lung	UBERON:0008948	67.19	gold quality
caput epididymis	UBERON:0004358	66.87	gold quality
left uterine tube	UBERON:0001303	66.68	gold quality
hypothalamus	UBERON:0001898	66.63	gold quality
bone marrow cell	CL:0002092	66.30	gold quality
left lobe of thyroid gland	UBERON:0001120	66.17	gold quality
right lobe of thyroid gland	UBERON:0001119	65.84	gold quality
thyroid gland	UBERON:0002046	65.81	gold quality
epithelium of nasopharynx	UBERON:0001951	65.72	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.62
E-GEOD-130148	yes	11.31
E-MTAB-8060	no	36.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting FHAD1, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-4266	98.53	67.29	1035

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhad1	ENSDARG00000056723
danio_rerio	si:dkey-163f12.6	ENSDARG00000094473
mus_musculus	Fhad1	ENSMUSG00000051435
rattus_norvegicus	Fhad1	ENSRNOG00000028064

Paralogs (1): CCDC27 (ENSG00000162592)

Protein

Protein identifiers

Forkhead-associated domain-containing protein 1 — B1AJZ9 (reviewed: B1AJZ9)

All UniProt accessions (10): B1AJZ9, A0A804HIA4, H0Y3C6, H0Y5P0, H0Y605, H0YCR1, H0YE38, H0YEU3, Q5JYW1, Q5JYW6

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of sperm motility and spermatocyte meiosis.

Subcellular location. Cell projection. Cilium. Flagellum.

Tissue specificity. Testis (at protein level).

Isoforms (3)

UniProt ID	Names	Canonical?
B1AJZ9-1	1	yes
B1AJZ9-3	3
B1AJZ9-4	4

RefSeq proteins (2): NP_001378886, NP_443161 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR052642	CC-FHA_domain	Family

Pfam: PF00498

UniProt features (22 total): coiled-coil region 5, compositionally biased region 5, region of interest 5, splice variant 2, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B1AJZ9-F1	71.77	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): BROWN_MYELOID_CELL_DEVELOPMENT_UP, LEIN_CHOROID_PLEXUS_MARKERS, GOCC_MOTILE_CILIUM, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chr1p36, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_D, RATTENBACHER_BOUND_BY_CELF1, GOCC_9PLUS2_MOTILE_CILIUM, FOXN3_TARGET_GENES, HAND1_TARGET_GENES, HDAC4_TARGET_GENES, HES2_TARGET_GENES, NFE2L1_TARGET_GENES, TOP2B_TARGET_GENES

GO Biological Process (2): apoptotic process (GO:0006915), spermatogenesis (GO:0007283)

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

GO Cellular Component (4): sperm flagellum (GO:0036126), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
developmental process involved in reproduction	1
male gamete generation	1
binding	1
9+2 motile cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
cellular anatomical structure	1

Protein interactions and networks

STRING

466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHAD1	KLHL8	Q9P2G9	668
FHAD1	PI15	O43692	540
FHAD1	ATP11A	P98196	507
FHAD1	ZNF407	Q9C0G0	499
FHAD1	SUSD4	Q5VX71	495
FHAD1	SEL1L3	Q68CR1	490
FHAD1	TTC34	A8MYJ7	484
FHAD1	FAM181B	A6NEQ2	452
FHAD1	OR5J2	Q8NH18	448
FHAD1	OR1N2	Q8NGR9	448
FHAD1	BCAS3	Q9H6U6	446
FHAD1	LRRC38	Q5VT99	426
FHAD1	HEPHL1	Q6MZM0	423
FHAD1	GLDC	P23378	418
FHAD1	TMEM101	Q96IK0	411

IntAct

5 interactions, top by confidence:

A	B	Type	Score
FHAD1	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
NEFM	FHAD1	psi-mi:“MI:0915”(physical association)	0.400
KLF8		psi-mi:“MI:0914”(association)	0.350
EPHA3	FHAD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): HIST2H2BF (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Affinity Capture-MS), FHAD1 (Cross-Linking-MS (XL-MS)), FHAD1 (Cross-Linking-MS (XL-MS)), ALOX12B (Cross-Linking-MS (XL-MS)), FHAD1 (Cross-Linking-MS (XL-MS)), FHAD1 (Proximity Label-MS)

ESM2 similar proteins: A0JMQ7, A0JMY4, A2AUM9, A2BDR7, A2BGP7, A6NI79, A6PWD2, A6QNP9, B1AJZ9, D3YV10, G9G127, O35550, O35551, O75330, O94986, P0CB05, Q05D60, Q0VFN8, Q0VFX2, Q15276, Q17QT2, Q3UPP8, Q498G2, Q4KLY0, Q4PJT6, Q4R703, Q4V7B0, Q5JU67, Q5NVN6, Q5U3A8, Q5U3Z6, Q5U4W1, Q5ZL12, Q66KE8, Q6DFC2, Q6DIS8, Q6IMY1, Q6NRC9, Q6P402, Q7M6Y5

Diamond homologs: A6PWD2, B1AJZ9, P66800, P9WGJ8, P9WGJ9, Q80U49, Q9Y4F5, A0QNG6, A0QYG2, B7SY83, O65934, P46014, P46017, P64898, P9WJA8, P9WJA9, P9WJB4, P9WJB5, Q4JVU0, Q6NHD4, Q8FTJ5, Q8NQJ3, Q9FIK2, A0JM08, Q498L0, Q5M9G6, Q5SW79, Q6A065, Q8BIZ6, Q8TAD8, Q8W4D8, Q96L14, Q9BWU0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	195
Likely benign	17
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
149960	GRCh38/hg38 1p36.21(chr1:13400935-15356944)x1	Likely pathogenic

SpliceAI

5951 predictions. Top by Δscore:

Variant	Effect	Δscore
1:15247391:GCCAG:G	donor_gain	1.0000
1:15251873:TACAG:T	donor_loss	1.0000
1:15251874:ACAG:A	donor_loss	1.0000
1:15251876:AG:A	donor_loss	1.0000
1:15251877:GG:G	donor_loss	1.0000
1:15251878:GT:G	donor_loss	1.0000
1:15251879:T:A	donor_loss	1.0000
1:15272321:A:AG	acceptor_gain	1.0000
1:15272322:G:GG	acceptor_gain	1.0000
1:15272528:CGG:C	donor_loss	1.0000
1:15272530:G:GC	donor_loss	1.0000
1:15272530:G:GG	donor_gain	1.0000
1:15272531:TGA:T	donor_loss	1.0000
1:15272532:GAG:G	donor_loss	1.0000
1:15289662:GCAAG:G	donor_gain	1.0000
1:15289665:AGGTA:A	donor_loss	1.0000
1:15289666:GG:G	donor_loss	1.0000
1:15289667:GT:G	donor_loss	1.0000
1:15289668:T:A	donor_loss	1.0000
1:15296668:T:A	acceptor_gain	1.0000
1:15308612:GATCA:G	acceptor_gain	1.0000
1:15312129:G:T	donor_gain	1.0000
1:15327051:T:TA	acceptor_gain	1.0000
1:15327054:T:A	acceptor_gain	1.0000
1:15327055:GCAGC:G	acceptor_loss	1.0000
1:15327057:A:AG	acceptor_gain	1.0000
1:15327058:G:GG	acceptor_gain	1.0000
1:15327058:GCT:G	acceptor_gain	1.0000
1:15327143:G:GA	donor_loss	1.0000
1:15327143:G:GG	donor_gain	1.0000

AlphaMissense

9859 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:15251798:T:C	L5P	0.997
1:15272347:G:C	A40P	0.997
1:15272392:G:C	D55H	0.997
1:15272393:A:C	D55A	0.997
1:15272420:T:A	V64D	0.997
1:15272348:C:A	A40E	0.996
1:15272387:T:C	L53P	0.996
1:15272456:T:A	L76H	0.996
1:15381343:G:C	R1283P	0.996
1:15272351:T:C	L41P	0.995
1:15272387:T:A	L53H	0.995
1:15251846:G:A	G21E	0.994
1:15272354:T:A	I42N	0.994
1:15272393:A:G	D55G	0.994
1:15272394:C:A	D55E	0.994
1:15272394:C:G	D55E	0.994
1:15272423:A:T	N65I	0.994
1:15272456:T:C	L76P	0.994
1:15272393:A:T	D55V	0.993
1:15272474:T:C	L82P	0.992
1:15272479:T:C	F84L	0.992
1:15272481:T:A	F84L	0.992
1:15272481:T:G	F84L	0.992
1:15381355:T:C	L1287P	0.992
1:15251843:T:A	I20N	0.991
1:15272414:C:A	T62K	0.991
1:15272416:T:C	F63L	0.991
1:15272418:T:A	F63L	0.991
1:15272418:T:G	F63L	0.991
1:15272480:T:C	F84S	0.991

dbSNP variants (sampled 300 via entrez): RS1000022013 (1:15252997 T>C), RS1000053098 (1:15375285 C>G), RS1000063159 (1:15334086 A>G,T), RS1000074432 (1:15297267 G>A,T), RS1000090329 (1:15289279 T>C), RS1000090748 (1:15337553 T>C,G), RS1000095550 (1:15334318 G>A), RS1000117157 (1:15370679 C>G), RS1000169729 (1:15380933 T>C), RS1000177528 (1:15270556 T>C), RS1000178066 (1:15326266 C>T), RS1000181293 (1:15258831 G>A,T), RS1000191855 (1:15269253 T>G), RS1000197308 (1:15390032 T>C), RS1000216158 (1:15310114 A>C,G)

Disease associations

OMIM: gene MIM:620889 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003226_3	Pelvic organ prolapse	7.000000e-07
GCST003560_7	Coronary artery aneurysm in Kawasaki disease	1.000000e-06
GCST004860_120	Alcoholic chronic pancreatitis	6.000000e-06
GCST004860_132	Alcoholic chronic pancreatitis	2.000000e-10
GCST004860_133	Alcoholic chronic pancreatitis	8.000000e-09
GCST004860_18	Alcoholic chronic pancreatitis	1.000000e-07
GCST004860_43	Alcoholic chronic pancreatitis	3.000000e-22
GCST004860_67	Alcoholic chronic pancreatitis	8.000000e-10
GCST004860_68	Alcoholic chronic pancreatitis	2.000000e-07
GCST009377_9	Bone mineral density	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007620	volumetric bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Silicon Dioxide	decreases expression, increases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
dimethylselenide	increases expression, increases oxidation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Methapyrilene	increases methylation	1
Ozone	increases oxidation, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	affects methylation	1
Hydroxyl Radical	increases expression, increases oxidation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8LD	Ubigene HCT 116 FHAD1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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