ANKEF1

Summary

ANKEF1 (ankyrin repeat and EF-hand domain containing 1, HGNC:15803) is a protein-coding gene on chromosome 20p12.2, encoding Ankyrin repeat and EF-hand domain-containing protein 1 (Q9NU02).

Predicted to enable calcium ion binding activity.

Source: NCBI Gene 63926 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 153 total — 9 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_022096

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15803
Approved symbol	ANKEF1
Name	ankyrin repeat and EF-hand domain containing 1
Location	20p12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21669, dJ839B4.6
Ensembl gene	ENSG00000132623
Ensembl biotype	protein_coding
Entrez	63926

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000378380, ENST00000378392, ENST00000437504, ENST00000488991, ENST00000937999, ENST00000966174

RefSeq mRNA: 3 — MANE Select: NM_022096 NM_001303472, NM_022096, NM_198798

CCDS: CCDS13108

Canonical transcript exons

ENST00000378392 — 11 exons

Exon	Start	End
ENSE00001477354	10035579	10035642
ENSE00001477365	10034987	10035333
ENSE00001888001	10055502	10058303
ENSE00003520744	10043122	10043321
ENSE00003531424	10054462	10054599
ENSE00003571338	10053112	10053275
ENSE00003621228	10045574	10045697
ENSE00003621601	10051663	10051889
ENSE00003652008	10044394	10044543
ENSE00003654766	10038258	10038647
ENSE00003682380	10049390	10050212

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 96.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7295 / max 54.6317, expressed in 1309 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183512	3.3637	986
183511	1.3119	872
183509	0.0403	16
183510	0.0135	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.56	gold quality
male germ cell	CL:0000015	92.52	gold quality
left testis	UBERON:0004533	84.38	gold quality
right testis	UBERON:0004534	84.11	gold quality
testis	UBERON:0000473	83.11	gold quality
islet of Langerhans	UBERON:0000006	82.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.79	gold quality
bronchial epithelial cell	CL:0002328	79.35	gold quality
esophagus squamous epithelium	UBERON:0006920	79.23	gold quality
pancreas	UBERON:0001264	78.03	gold quality
epithelium of esophagus	UBERON:0001976	77.05	gold quality
body of pancreas	UBERON:0001150	76.83	gold quality
epithelium of bronchus	UBERON:0002031	76.45	gold quality
bronchus	UBERON:0002185	76.08	gold quality
squamous epithelium	UBERON:0006914	75.31	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.01	gold quality
epithelium of nasopharynx	UBERON:0001951	74.91	gold quality
palpebral conjunctiva	UBERON:0001812	74.28	gold quality
adrenal tissue	UBERON:0018303	73.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	73.98	gold quality
gingival epithelium	UBERON:0001949	73.30	silver quality
cerebellar vermis	UBERON:0004720	73.19	gold quality
gingiva	UBERON:0001828	73.00	silver quality
colonic mucosa	UBERON:0000317	72.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	72.16	gold quality
germinal epithelium of ovary	UBERON:0001304	71.48	gold quality
choroid plexus epithelium	UBERON:0003911	71.16	silver quality
oocyte	CL:0000023	71.02	gold quality
rectum	UBERON:0001052	70.57	gold quality
secondary oocyte	CL:0000655	70.34	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting ANKEF1, 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-5692A	100.00	74.40	6850
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3667-3P	99.99	67.17	1636
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-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-539-5P	99.93	70.30	2855

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankef1a	ENSDARG00000019135
danio_rerio	ankef1b	ENSDARG00000060211
mus_musculus	Ankef1	ENSMUSG00000074771
rattus_norvegicus	Ankef1	ENSRNOG00000005792

Protein

Protein identifiers

Ankyrin repeat and EF-hand domain-containing protein 1 — Q9NU02 (reviewed: Q9NU02)

Alternative names: Ankyrin repeat domain-containing protein 5

All UniProt accessions (1): Q9NU02

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (3): NP_001290401, NP_071379, NP_942093 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR052801	Ankyrin-EF-hand	Family

Pfam: PF12796

UniProt features (15 total): repeat 8, sequence variant 5, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NU02-F1	80.95	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MODULE_397, CHEN_METABOLIC_SYNDROM_NETWORK, OISHI_CHOLANGIOMA_STEM_CELL_LIKE_UP, FOXN3_TARGET_GENES, HDAC4_TARGET_GENES, HES2_TARGET_GENES, HMG20B_TARGET_GENES, NAB2_TARGET_GENES, ZNF8_TARGET_GENES, MIR4262, GSE10325_BCELL_VS_MYELOID_UP

GO Biological Process (0):

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	1
binding	1

Protein interactions and networks

STRING

803 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKEF1	CLBA1	Q96F83	554
ANKEF1	GTPBP10	A4D1E9	431
ANKEF1	HCFC1R1	Q9NWW0	421
ANKEF1	SLX4IP	Q5VYV7	412
ANKEF1	DPEP3	Q9H4B8	399
ANKEF1	OAZ3	Q9UMX2	399
ANKEF1	ZG16B	Q96DA0	398
ANKEF1	ZNF226	Q9NYT6	379
ANKEF1	ZBTB42	B2RXF5	370
ANKEF1	CIAO2B	Q9Y3D0	370
ANKEF1	MINDY3	Q9H8M7	367
ANKEF1	TEX2	Q8IWB9	353
ANKEF1	TPGS2	Q68CL5	353
ANKEF1	SPATA21	Q7Z572	349
ANKEF1	PAK5	Q9P286	336

IntAct

40 interactions, top by confidence:

A	B	Type	Score
ANKEF1	CASP6	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	CCK	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	P4HB	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	CLASRP	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	PRPF40A	psi-mi:“MI:0915”(physical association)	0.560
ANKEF1	COQ8A	psi-mi:“MI:0915”(physical association)	0.560
SSBP3	ANKEF1	psi-mi:“MI:0915”(physical association)	0.370
ANKEF1	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
JMJD6	ANKEF1	psi-mi:“MI:0915”(physical association)	0.370
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	PDHX	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): ANKEF1 (Affinity Capture-MS), ANKEF1 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), CIRH1A (Affinity Capture-MS), USP46 (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), NXN (Affinity Capture-MS), CALCB (Affinity Capture-MS), ANKEF1 (Two-hybrid), ANKEF1 (Affinity Capture-MS), ANKEF1 (Cross-Linking-MS (XL-MS)), ANKEF1 (Affinity Capture-MS), STX7 (Cross-Linking-MS (XL-MS)), ANKEF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A2AGL3, A7MB89, B0LPN4, E9Q401, O60733, P30957, P42694, P49754, P97570, P97819, Q15413, Q29RM5, Q2KIX2, Q2T9K6, Q32PW3, Q3SX45, Q4V890, Q59H18, Q5F361, Q5GIG6, Q5KU39, Q5RF15, Q5U2S6, Q5ZKK2, Q66H07, Q66H63, Q6B858, Q6DFV5, Q6NYU2, Q7T3P8, Q7TQP6, Q8C0T1, Q8CEF1, Q8K0L0, Q8K114, Q8TC84, Q91W86, Q92736

Diamond homologs: G3I6Z6, G5EGA3, O90760, Q01705, Q04861, Q05823, Q07008, Q3UUF8, Q4UMP3, Q5UPG0, Q5UPG6, Q5UQ58, Q9D2J7, Q9J513, Q9J5H7, Q9NU02, B2RXR6, O89019, P33520, Q08353, Q3U0L2, Q4FE45, Q4R7L8, Q5RD76, Q5ZLC8, Q65XV2, Q68DC2, Q6JAN1, Q6KAE5, Q7EZ44, Q8N8A2, Q8UVC3, Q93650, Q94B55, Q94CT7, Q96KQ7, Q9BQG2, Q9BZL4, Q9DCN1, Q9VCA8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	1
Uncertain significance	132
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
145966	GRCh38/hg38 20p12.3-12.1(chr20:6617695-13392559)x1	Pathogenic
146031	GRCh38/hg38 20p12.2-12.1(chr20:9550975-12083434)x1	Pathogenic
3062400	GRCh37/hg19 20p12.3-12.2(chr20:7856703-11991178)x1	Pathogenic
3062413	GRCh37/hg19 20p12.2(chr20:9596286-10678665)x1	Pathogenic
394208	GRCh37/hg19 20p13-12.1(chr20:4392930-12667768)x1	Pathogenic
4072094	NC_000020.10:g.9288451_10654188del	Pathogenic
4075892	GRCh37/hg19 20p12.3-12.1(chr20:8662320-12495149)x1	Pathogenic
564644	GRCh37/hg19 20p12.3-12.1(chr20:7604120-14739025)x3	Pathogenic
58946	GRCh38/hg38 20p12.3-12.2(chr20:7566644-11028694)x1	Pathogenic
3338444	GRCh37/hg19 20p12.3-12.1(chr20:5454270-13610745)x1	Likely pathogenic

SpliceAI

1653 predictions. Top by Δscore:

Variant	Effect	Δscore
20:10043221:G:GT	donor_gain	1.0000
20:10043222:A:T	donor_gain	1.0000
20:10043269:A:G	donor_gain	1.0000
20:10043296:G:GT	donor_gain	1.0000
20:10043317:ACTCA:A	donor_gain	1.0000
20:10043318:C:G	donor_gain	1.0000
20:10043322:G:GG	donor_gain	1.0000
20:10044530:G:GT	donor_gain	1.0000
20:10044541:GAT:G	donor_gain	1.0000
20:10044544:G:GG	donor_gain	1.0000
20:10050267:G:GT	donor_gain	1.0000
20:10051662:GA:G	acceptor_gain	1.0000
20:10051888:AGGTA:A	donor_loss	1.0000
20:10051890:G:GA	donor_loss	1.0000
20:10051891:T:A	donor_loss	1.0000
20:10053100:AT:A	acceptor_gain	1.0000
20:10053101:T:G	acceptor_gain	1.0000
20:10053101:T:TA	acceptor_gain	1.0000
20:10053107:A:AG	acceptor_gain	1.0000
20:10053107:AACAG:A	acceptor_gain	1.0000
20:10053108:A:G	acceptor_gain	1.0000
20:10053108:ACAG:A	acceptor_gain	1.0000
20:10053108:ACAGG:A	acceptor_gain	1.0000
20:10053109:CA:C	acceptor_loss	1.0000
20:10053109:CAGGG:C	acceptor_gain	1.0000
20:10053110:A:AG	acceptor_gain	1.0000
20:10053110:A:C	acceptor_loss	1.0000
20:10053110:AG:A	acceptor_gain	1.0000
20:10053110:AGG:A	acceptor_gain	1.0000
20:10053110:AGGG:A	acceptor_gain	1.0000

AlphaMissense

5110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:10051717:C:G	C566W	0.997
20:10051713:C:A	A565E	0.996
20:10044521:C:A	A225D	0.995
20:10044524:C:A	A226D	0.995
20:10050168:T:G	C533W	0.995
20:10051715:T:C	C566R	0.995
20:10051716:G:A	C566Y	0.995
20:10050200:T:C	L544P	0.994
20:10051811:G:C	A598P	0.994
20:10051848:T:C	L610P	0.994
20:10038566:G:C	A89P	0.993
20:10044523:G:C	A226P	0.993
20:10045695:G:C	R273P	0.993
20:10050166:T:C	C533R	0.993
20:10053133:C:A	A631E	0.993
20:10045650:C:A	A258D	0.992
20:10050092:T:C	L508P	0.991
20:10050167:G:A	C533Y	0.991
20:10051694:T:A	W559R	0.991
20:10051694:T:C	W559R	0.991
20:10051800:C:A	P594H	0.991
20:10051812:C:A	A598D	0.991
20:10044449:T:A	V201D	0.990
20:10045653:C:A	A259D	0.990
20:10053132:G:C	A631P	0.990
20:10044458:T:A	I204K	0.989
20:10045652:G:C	A259P	0.989
20:10049441:C:A	A291D	0.989
20:10050155:T:C	L529P	0.989
20:10050163:G:C	A532P	0.989

dbSNP variants (sampled 300 via entrez): RS1000206449 (20:10037553 G>A), RS1000358523 (20:10055959 T>C), RS1000380410 (20:10044277 A>T), RS1000412324 (20:10056130 A>G), RS1000438460 (20:10050737 C>T), RS1000542064 (20:10036391 G>A), RS1000549884 (20:10037085 A>C,G,T), RS1000634569 (20:10049349 G>A), RS1000719833 (20:10043052 A>C,G), RS1000822426 (20:10049055 T>A), RS1001214028 (20:10036892 C>T), RS1001384989 (20:10037250 G>A), RS1001517576 (20:10043453 G>A), RS1001586503 (20:10048595 C>T), RS1001732509 (20:10056679 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616330, MIM:118450

GenCC curated gene-disease

Mondo (2): congenital myasthenic syndrome 18 (MONDO:0014590), Alagille syndrome due to a JAG1 point mutation (MONDO:0016862)

Orphanet (3): Congenital myasthenic syndrome (Orphanet:590), Alagille syndrome due to a JAG1 point mutation (Orphanet:261619), Alagille syndrome (Orphanet:52)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007898_6	Fasting blood insulin	2.000000e-11
GCST008162_28	Hip circumference	4.000000e-06
GCST009391_751	Metabolite levels	1.000000e-06
GCST010149_1	Brain imaging measurements (variance)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010390	sphingomyelin 14:0 measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases mutagenesis	4
Valproic Acid	affects cotreatment, increases expression	4
entinostat	increases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
sotorasib	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

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