ANKRD49

Summary

ANKRD49 (ankyrin repeat domain 49, HGNC:25970) is a protein-coding gene on chromosome 11q21, encoding Ankyrin repeat domain-containing protein 49 (Q8WVL7). Induces HBG1 expression. It is a selective cancer dependency (DepMap: 34.1% of cell lines).

Involved in positive regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 54851 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 34.1% of screened cell lines
• MANE Select transcript: NM_017704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25970
Approved symbol	ANKRD49
Name	ankyrin repeat domain 49
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20189, FGIF, GBIF
Ensembl gene	ENSG00000168876
Ensembl biotype	protein_coding
OMIM	619571
Entrez	54851

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000302755, ENST00000534911, ENST00000535502, ENST00000538535, ENST00000539883, ENST00000540349, ENST00000541144, ENST00000544253, ENST00000544514, ENST00000544612, ENST00000545130, ENST00000852022

RefSeq mRNA: 1 — MANE Select: NM_017704 NM_017704

CCDS: CCDS8300

Canonical transcript exons

ENST00000544612 — 3 exons

Exon	Start	End
ENSE00001121843	94496604	94496951
ENSE00001195463	94493984	94494035
ENSE00002307426	94498071	94499578

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 92.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9183 / max 172.2434, expressed in 1677 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116256	8.7358	1674
116255	0.1825	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.25	gold quality
cardia of stomach	UBERON:0001162	92.24	gold quality
epithelium of nasopharynx	UBERON:0001951	91.97	gold quality
nasopharynx	UBERON:0001728	91.95	gold quality
pylorus	UBERON:0001166	91.18	gold quality
hair follicle	UBERON:0002073	90.49	gold quality
pancreatic ductal cell	CL:0002079	90.48	gold quality
lymph node	UBERON:0000029	89.62	gold quality
endothelial cell	CL:0000115	89.06	gold quality
superficial temporal artery	UBERON:0001614	89.02	gold quality
tongue squamous epithelium	UBERON:0006919	89.02	gold quality
bone marrow	UBERON:0002371	88.98	gold quality
mononuclear cell	CL:0000842	88.49	gold quality
monocyte	CL:0000576	88.47	gold quality
leukocyte	CL:0000738	88.33	gold quality
trabecular bone tissue	UBERON:0002483	88.04	gold quality
rectum	UBERON:0001052	87.82	gold quality
colonic mucosa	UBERON:0000317	87.77	gold quality
jejunal mucosa	UBERON:0000399	87.67	gold quality
body of pancreas	UBERON:0001150	87.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.32	gold quality
tonsil	UBERON:0002372	87.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.26	gold quality
granulocyte	CL:0000094	87.24	gold quality
superior surface of tongue	UBERON:0007371	87.10	gold quality
ileal mucosa	UBERON:0000331	86.94	gold quality
spleen	UBERON:0002106	86.92	gold quality
urethra	UBERON:0000057	86.87	gold quality
renal medulla	UBERON:0000362	86.79	gold quality
palpebral conjunctiva	UBERON:0001812	86.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting ANKRD49, 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-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8087	99.90	69.55	1351

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• The research findings implicate that ANKRD49 promotes the proliferation of human malignant glioma cells. (PMID:28694302)
• The results of the present study highlighted an important role of the ANKRD49 protein in the progression of gastric cancer. The ANKRD49 protein could act as a potential biomarker for prognosis evaluation of gastric cancer and may be used as a molecular target for gastric cancer treatment. (PMID:29865034)
• these results suggest that ANKRD49 plays an important role in reducing intrinsic apoptosis of GC-1 cells by modulating the NF-kappaB signaling pathway. (PMID:30798416)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd49	ENSDARG00000023508
mus_musculus	Ankrd49	ENSMUSG00000031931
rattus_norvegicus	Ankrd49	ENSRNOG00000009233
drosophila_melanogaster	Ankrd49	FBGN0261881
caenorhabditis_elegans		WBGENE00017831

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 49 — Q8WVL7 (reviewed: Q8WVL7)

Alternative names: Fetal globin-inducing factor

All UniProt accessions (6): Q8WVL7, F5GWD9, F5H227, F5H3B3, F5H7L0, F6R851

UniProt curated annotations — full annotation on UniProt →

Function. Induces HBG1 expression. May have a role in spermatogenesis where it promotes autophagy in response to serum starvation, via the NF-kappaB pathway.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed in fetus, at a high level in fetal liver, brain and lung.

RefSeq proteins (1): NP_060174* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF12796

UniProt features (8 total): repeat 4, sequence conflict 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVL7-F1	81.73	0.60

Functional residue map

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

Post-translational modifications (1): 49

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GOBP_MALE_GAMETE_GENERATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, ACEVEDO_LIVER_CANCER_UP, RIZ_ERYTHROID_DIFFERENTIATION, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, MARSON_BOUND_BY_E2F4_UNSTIMULATED, chr11q21, ZHAN_MULTIPLE_MYELOMA_MS_DN, GTCAACC_MIR3805P, MIKKELSEN_MCV6_LCP_WITH_H3K4ME3, MARTENS_TRETINOIN_RESPONSE_DN

GO Biological Process (3): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), positive regulation of DNA-templated transcription (GO:0045893)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD49	TRIT1	Q9H3H1	922
ANKRD49	MT-CO1	P00395	547
ANKRD49	CSNK1E	P49674	526
ANKRD49	SLC25A19	Q9HC21	526
ANKRD49	CSNK1D	P48730	505
ANKRD49	XYLB	O75191	490
ANKRD49	MSANTD4	Q8NCY6	489
ANKRD49	DDX6	P26196	489
ANKRD49	FAM110B	Q8TC76	472
ANKRD49	KCTD10	Q9H3F6	446
ANKRD49	FASN	P49327	436
ANKRD49	MRPL10	Q7Z7H8	417
ANKRD49	LYSMD1	Q96S90	415
ANKRD49	BTG2	P78543	410
ANKRD49	XKR4	Q5GH76	399
ANKRD49	GTF2E2	P29084	399

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
ANKRD49	FKBPL	psi-mi:“MI:0915”(physical association)	0.860
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
CSNK1E	PER2	psi-mi:“MI:0914”(association)	0.850
HIF1AN	ANKRD49	psi-mi:“MI:0210”(hydroxylation reaction)	0.810
CSNK1D	PER2	psi-mi:“MI:0914”(association)	0.810
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
ANKRD49	CSNK1E	psi-mi:“MI:0914”(association)	0.640
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
ANKRD49	SMARCD1	psi-mi:“MI:0915”(physical association)	0.600
SMARCD1	ANKRD49	psi-mi:“MI:0915”(physical association)	0.600
ANKRD49	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
RAN	ANKRD49	psi-mi:“MI:0915”(physical association)	0.400
CFTR	ANKRD49	psi-mi:“MI:0915”(physical association)	0.370
ANKRD49	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
HIF1AN	ARID1A	psi-mi:“MI:0914”(association)	0.350
CPSF4	P4HA2	psi-mi:“MI:0914”(association)	0.350
CSNK1D	PER1	psi-mi:“MI:0914”(association)	0.350
ANKRD49	RCBTB2	psi-mi:“MI:0914”(association)	0.350
CSNK1D	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CSNK1A1L	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FAM107A	SPTB	psi-mi:“MI:0914”(association)	0.350
MOCS1	TMF1	psi-mi:“MI:0914”(association)	0.350
ANKRD49	SHTN1	psi-mi:“MI:0914”(association)	0.350
ANKRD49		psi-mi:“MI:0914”(association)	0.350
STARD3NL	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
FKBPL	EL52	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): ANKRD49 (Affinity Capture-RNA), ANKRD49 (Affinity Capture-RNA), ANKRD49 (Affinity Capture-RNA), FKBPL (Affinity Capture-MS), FKBPL (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), ANKRD49 (Affinity Capture-MS), CSNK1E (Affinity Capture-MS), ANKRD49 (Affinity Capture-MS), CPNE4 (Affinity Capture-MS), RCBTB2 (Affinity Capture-MS), ANKRD49 (Affinity Capture-MS), ANKRD49 (Two-hybrid), ANKRD49 (Two-hybrid), FKBPL (Two-hybrid)

ESM2 similar proteins: A0M8T3, A0PJZ0, A1X154, A4D7T3, A6NHY2, C7B178, P57078, Q00PJ3, Q07DV3, Q07DX6, Q07DY6, Q07DZ7, Q07E17, Q07E30, Q07E43, Q09YH1, Q09YI3, Q09YJ5, Q09YK6, Q09YN0, Q108U1, Q14DN9, Q2IBB1, Q2IBB4, Q2IBE3, Q2IBF5, Q2IBG0, Q2QL84, Q2QLA4, Q2QLB5, Q2QLC6, Q2QLG0, Q2QLH1, Q4R3S3, Q5EA33, Q5RCK5, Q8NFD2, Q8VD46, Q8VE42, Q8WMX6

Diamond homologs: G0LXV8, L7X8P2, L7XCU0, L7XDS4, P0DJE3, P0DJE5, P23631, Q02989, Q09701, Q17QS6, Q21209, Q25338, Q5EA33, Q755Y0, Q862Z2, Q8WVL7, Q8WWX0, Q9D1A4, Q9XZC0, A2RUV0, G3I6Z6, O35516, P0DJE7, P21783, P42773, P83757, Q01705, Q04721, Q07008, Q54HW1, Q875S9, Q9QW30, Q0VCS9, Q3TPE9, Q5ZMD2, Q8IV38, B0G124, B4E2M5, C7B178, O43150

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	18
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3063184	GRCh37/hg19 11q21(chr11:94130773-94280193)x1	Pathogenic

SpliceAI

402 predictions. Top by Δscore:

Variant	Effect	Δscore
11:94497433:C:CG	donor_gain	1.0000
11:94498069:A:AG	acceptor_gain	1.0000
11:94498070:G:GC	acceptor_gain	1.0000
11:94498070:GC:G	acceptor_gain	1.0000
11:94498070:GCT:G	acceptor_gain	1.0000
11:94498070:GCTT:G	acceptor_gain	1.0000
11:94498070:GCTTA:G	acceptor_gain	1.0000
11:94494033:CAGGT:C	donor_loss	0.9900
11:94494034:AG:A	donor_loss	0.9900
11:94494035:GGTG:G	donor_loss	0.9900
11:94494037:T:A	donor_loss	0.9900
11:94496598:TTTCA:T	acceptor_loss	0.9900
11:94496599:TTCA:T	acceptor_loss	0.9900
11:94496600:TCAGA:T	acceptor_loss	0.9900
11:94496601:CA:C	acceptor_loss	0.9900
11:94496602:A:AG	acceptor_gain	0.9900
11:94496602:AGATC:A	acceptor_loss	0.9900
11:94496603:G:GG	acceptor_gain	0.9900
11:94497433:C:G	donor_gain	0.9900
11:94493998:G:GT	donor_gain	0.9800
11:94496948:TCGGG:T	donor_loss	0.9800
11:94496949:CGG:C	donor_loss	0.9800
11:94496953:T:G	donor_loss	0.9800
11:94496590:ATTT:A	acceptor_loss	0.9700
11:94496878:G:GA	donor_gain	0.9700
11:94496905:A:T	donor_gain	0.9700
11:94496950:GG:G	donor_gain	0.9700
11:94496951:GG:G	donor_gain	0.9700
11:94496974:G:T	donor_gain	0.9700
11:94496603:GATCT:G	acceptor_gain	0.9600

AlphaMissense

1591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:94498192:T:C	L127P	0.996
11:94498291:T:C	L160S	0.996
11:94498257:T:C	C149R	0.995
11:94498259:T:G	C149W	0.995
11:94498155:G:C	A115P	0.993
11:94498258:G:A	C149Y	0.993
11:94498294:T:C	L161P	0.993
11:94496938:C:A	A82D	0.992
11:94498153:G:C	R114P	0.992
11:94498156:C:A	A115E	0.992
11:94498159:C:A	A116D	0.992
11:94498147:T:A	L112H	0.991
11:94498158:G:C	A116P	0.991
11:94498243:C:A	P144H	0.991
11:94498255:C:A	A148D	0.991
11:94496937:G:C	A82P	0.990
11:94498342:C:A	P177H	0.990
11:94496934:G:C	A81P	0.989
11:94498254:G:C	A148P	0.988
11:94498351:T:C	L180P	0.988
11:94498246:T:C	L145P	0.987
11:94498356:G:C	A182P	0.987
11:94498357:C:A	A182D	0.987
11:94498459:C:A	A216D	0.987
11:94498282:C:A	A157D	0.986
11:94498353:G:C	A181P	0.986
11:94498390:T:C	L193P	0.986
11:94498393:T:C	L194P	0.986
11:94496950:G:C	R86P	0.985
11:94498147:T:C	L112P	0.985

dbSNP variants (sampled 300 via entrez): RS1000055780 (11:94495642 G>A), RS1000792942 (11:94493316 AT>A,ATT), RS1000861327 (11:94493533 C>A), RS1000951914 (11:94493994 C>A,T), RS1001237874 (11:94496193 T>C), RS1001272719 (11:94495309 T>G), RS1002078668 (11:94493905 G>A), RS1002639414 (11:94494507 C>T), RS1002792650 (11:94499648 G>A,T), RS1002940181 (11:94497457 GTAAAC>G), RS1003316499 (11:94499974 T>G), RS1003755171 (11:94495024 CTGAT>C), RS1004052567 (11:94494303 C>T), RS1004846317 (11:94499669 A>C), RS1004983255 (11:94499186 T>G)

Disease associations

OMIM: gene MIM:619571 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance, increases expression	3
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
alpha phellandrene	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression, increases abundance	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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