ANKDD1B

Summary

ANKDD1B (ankyrin repeat and death domain containing 1B, HGNC:32525) is a protein-coding gene on chromosome 5q13.3, encoding Ankyrin repeat and death domain-containing protein 1B (A6NHY2).

Predicted to be involved in signal transduction.

Source: NCBI Gene 728780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ankylosing spondylitis (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_001276713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32525
Approved symbol	ANKDD1B
Name	ankyrin repeat and death domain containing 1B
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189045
Ensembl biotype	protein_coding
OMIM	619920
Entrez	728780

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

ENST00000504514, ENST00000506596, ENST00000594319, ENST00000601380, ENST00000672135, ENST00000672390, ENST00000672397, ENST00000672400, ENST00000672660, ENST00000672802, ENST00000672844, ENST00000672850, ENST00000673223, ENST00000673225, ENST00000885186, ENST00000885187, ENST00000885188, ENST00000885189, ENST00000885190, ENST00000885191, ENST00000960210, ENST00000960211

RefSeq mRNA: 1 — MANE Select: NM_001276713 NM_001276713

CCDS: CCDS64180

Canonical transcript exons

ENST00000601380 — 14 exons

Exon	Start	End
ENSE00002020975	75620315	75620413
ENSE00002027494	75625647	75625745
ENSE00002087583	75616804	75616907
ENSE00002288620	75634898	75634996
ENSE00002321162	75625851	75625955
ENSE00003023771	75669252	75669383
ENSE00003365306	75611453	75611827
ENSE00003488221	75653142	75653240
ENSE00003513870	75656029	75656127
ENSE00003534600	75670979	75671846
ENSE00003616309	75663394	75663489
ENSE00003625894	75635784	75635882
ENSE00003626805	75659283	75659381
ENSE00003653910	75666792	75666993

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 92.23.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.80	gold quality
rectum	UBERON:0001052	78.79	gold quality
transverse colon	UBERON:0001157	78.33	gold quality
metanephros cortex	UBERON:0010533	77.83	gold quality
mucosa of transverse colon	UBERON:0004991	76.70	gold quality
fallopian tube	UBERON:0003889	76.34	gold quality
cortex of kidney	UBERON:0001225	75.16	gold quality
endometrium	UBERON:0001295	74.36	gold quality
sural nerve	UBERON:0015488	73.78	gold quality
adult mammalian kidney	UBERON:0000082	73.47	gold quality
kidney	UBERON:0002113	73.13	gold quality
colon	UBERON:0001155	72.40	gold quality
right lung	UBERON:0002167	72.17	gold quality
mucosa of stomach	UBERON:0001199	71.34	gold quality
intestine	UBERON:0000160	71.00	gold quality
adrenal tissue	UBERON:0018303	70.55	gold quality
nucleus accumbens	UBERON:0001882	70.15	gold quality
left uterine tube	UBERON:0001303	69.65	gold quality
vagina	UBERON:0000996	68.60	gold quality
tibial nerve	UBERON:0001323	68.37	gold quality
monocyte	CL:0000576	68.31	gold quality
right adrenal gland	UBERON:0001233	68.13	gold quality
right adrenal gland cortex	UBERON:0035827	68.09	gold quality
upper lobe of left lung	UBERON:0008952	68.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.59	gold quality
caudate nucleus	UBERON:0001873	67.43	gold quality
lung	UBERON:0002048	67.19	gold quality
left adrenal gland	UBERON:0001234	67.18	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.06
E-CURD-10	no	52.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting ANKDD1B, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-140-5P	99.44	67.20	792

Literature-anchored findings (GeneRIF, showing 1)

• Risk of migraine contributed by genetic polymorphisms of ANKDD1B gene: a case-control study based on Chinese Han population. (PMID:34669083)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankdd1b	ENSDARG00000025866
mus_musculus	Ankdd1b	ENSMUSG00000047117
rattus_norvegicus	Ankdd1b	ENSRNOG00000025377

Paralogs (1): ANKDD1A (ENSG00000166839)

Protein

Protein identifiers

Ankyrin repeat and death domain-containing protein 1B — A6NHY2 (reviewed: A6NHY2)

All UniProt accessions (11): A0A5F9ZH51, A0A5F9ZH63, A0A5F9ZHD3, A0A5F9ZHN1, A0A5F9ZHN3, A0A5F9ZHP8, A0A5F9ZHS6, A0A5F9ZHU1, A0A5F9ZHV6, A0A5F9ZI24, A6NHY2

RefSeq proteins (1): NP_001263642* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR052457	Ankyrin-DD_containing_protein	Family

Pfam: PF00023, PF12796

UniProt features (12 total): repeat 10, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NHY2-F1	83.90	0.68

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, ZNF766_TARGET_GENES, ZNF843_TARGET_GENES, MIR545_3P, MIR548AV_5P_MIR548K, MIR8054, MIR3124_3P, MIR452_3P, MIR1246, GSE13306_TREG_VS_TCONV_SPLEEN_UP, GSE14308_TH2_VS_INDUCED_TREG_DN, MANNE_COVID19_NONICU_VS_HEALTHY_DONOR_PLATELETS_DN, MANNE_COVID19_ICU_VS_HEALTHY_DONOR_PLATELETS_DN, MANNE_COVID19_COMBINED_COHORT_VS_HEALTHY_DONOR_PLATELETS_DN, GAO_LARGE_INTESTINE_ADULT_CE_OLFM4HIGH_STEM_CELL

GO Biological Process (1): signal transduction (GO:0007165)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
binding	1

Protein interactions and networks

STRING

1055 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKDD1B	MOB3C	Q70IA8	535
ANKDD1B	ZNF787	Q6DD87	519
ANKDD1B	CDH24	Q86UP0	518
ANKDD1B	OR51Q1	Q8NH59	462
ANKDD1B	MAMDC4	Q6UXC1	448
ANKDD1B	PRRT4	C9JH25	447
ANKDD1B	KCNK5	O95279	421
ANKDD1B	MROH2A	A6NES4	414
ANKDD1B	OR2L8	Q8NGY9	398
ANKDD1B	MAGEB16	A2A368	391
ANKDD1B	FOXD4L3	Q6VB84	380
ANKDD1B	TMEM174	Q8WUU8	379
ANKDD1B	RFPL3	O75679	375
ANKDD1B	MS4A14	Q96JA4	374
ANKDD1B	ARMH4	Q86TY3	367

IntAct

0 interactions, top by confidence:

BioGRID (1): ANKDD1B (Affinity Capture-MS)

ESM2 similar proteins: A0JM23, A0M8T3, A1X154, A4D7T3, A6H6E9, A6NHY2, P0CI65, Q008S8, Q00PJ3, Q07DV3, Q07DX6, Q07DY6, Q07DZ7, Q07E17, Q07E30, Q07E43, Q09YH1, Q09YI3, Q09YJ5, Q09YK6, Q09YN0, Q108U1, Q14DN9, Q15052, Q2IBB1, Q2IBB4, Q2IBE3, Q2IBF5, Q2IBG0, Q2QL84, Q2QLA4, Q2QLB5, Q2QLC6, Q2QLG0, Q2QLH1, Q32NR4, Q3UMR0, Q5JTW2, Q5REW9, Q5XXR3

Diamond homologs: A6NHY2, Q14DN9, Q495B1, Q9GKW8, P83757, Q03017, Q6KAE5, Q8N9U9, Q9H2K2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	2
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2773 predictions. Top by Δscore:

Variant	Effect	Δscore
5:75611823:GCTCC:G	donor_gain	1.0000
5:75616802:A:AG	acceptor_gain	1.0000
5:75616803:G:GG	acceptor_gain	1.0000
5:75616803:GT:G	acceptor_gain	1.0000
5:75616803:GTA:G	acceptor_gain	1.0000
5:75625639:T:TA	acceptor_gain	1.0000
5:75625640:G:A	acceptor_gain	1.0000
5:75640602:T:A	acceptor_gain	1.0000
5:75653238:G:GT	donor_gain	1.0000
5:75653241:G:GG	donor_gain	1.0000
5:75659276:AT:A	acceptor_gain	1.0000
5:75659277:T:G	acceptor_gain	1.0000
5:75659277:T:TA	acceptor_gain	1.0000
5:75659381:GGT:G	donor_loss	1.0000
5:75659382:G:C	donor_loss	1.0000
5:75659382:G:GG	donor_gain	1.0000
5:75674577:TG:T	acceptor_gain	1.0000
5:75677882:T:TA	donor_gain	1.0000
5:75677947:CATA:C	acceptor_gain	1.0000
5:75677949:TA:T	acceptor_gain	1.0000
5:75677951:C:CC	acceptor_gain	1.0000
5:75611828:G:GG	donor_gain	0.9900
5:75618591:A:G	donor_gain	0.9900
5:75625474:T:G	donor_gain	0.9900
5:75640599:T:TA	acceptor_gain	0.9900
5:75640607:T:TA	acceptor_gain	0.9900
5:75653236:TGG:T	donor_gain	0.9900
5:75653237:GGAA:G	donor_gain	0.9900
5:75653238:GAA:G	donor_gain	0.9900
5:75656621:TTA:T	donor_gain	0.9900

AlphaMissense

3505 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:75666951:T:C	F451L	0.899
5:75666953:T:A	F451L	0.899
5:75666953:T:G	F451L	0.899
5:75666840:T:C	F414L	0.894
5:75666842:C:A	F414L	0.894
5:75666842:C:G	F414L	0.894
5:75620336:T:C	F107L	0.893
5:75620338:T:A	F107L	0.893
5:75620338:T:G	F107L	0.893
5:75620376:T:C	L120S	0.881
5:75616824:T:C	F72L	0.879
5:75616826:T:A	F72L	0.879
5:75616826:T:G	F72L	0.879
5:75620372:T:C	F119L	0.877
5:75620374:C:A	F119L	0.877
5:75620374:C:G	F119L	0.877
5:75616837:C:A	A76D	0.870
5:75620322:G:C	R102P	0.869
5:75620340:C:A	A108E	0.866
5:75616833:G:C	A75P	0.864
5:75625876:C:A	A174D	0.856
5:75625672:C:A	A141E	0.848
5:75625912:T:C	L186P	0.842
5:75625675:C:A	A142D	0.841
5:75620328:C:A	A104D	0.836
5:75634913:T:C	F206L	0.836
5:75634915:T:A	F206L	0.836
5:75634915:T:G	F206L	0.836
5:75669263:T:C	F469L	0.831
5:75669265:C:A	F469L	0.831

dbSNP variants (sampled 300 via entrez): RS1000034158 (5:75647788 A>G), RS1000046954 (5:75623794 T>C,G), RS1000109648 (5:75630809 A>G), RS1000110971 (5:75652048 C>T), RS1000245784 (5:75637200 G>A), RS1000291034 (5:75615699 T>TGTGTCC), RS1000292377 (5:75666186 T>C), RS1000355560 (5:75633359 T>A), RS1000378362 (5:75649384 T>C), RS1000431162 (5:75626864 A>G), RS1000475505 (5:75649082 C>T), RS1000481401 (5:75633528 G>A,C), RS1000506206 (5:75654865 G>C), RS1000535426 (5:75655036 C>T), RS1000650576 (5:75612191 T>A,G)

Disease associations

OMIM: gene MIM:619920 | disease phenotypes: MIM:268800

GenCC curated gene-disease

Disease	Classification	Inheritance
ankylosing spondylitis	Limited	Autosomal dominant

Mondo (2): Sandhoff disease (MONDO:0010006), ankylosing spondylitis (MONDO:0005306)

Orphanet (1): Sandhoff disease (Orphanet:796)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005830_127	Hand grip strength	8.000000e-10
GCST006034_33	Total cholesterol levels	3.000000e-36
GCST010060_14	Cholesterol	4.000000e-08
GCST90002401_161	Platelet distribution width	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0004574	total cholesterol measurement
EFO:0007984	platelet component distribution width

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D012497	Sandhoff Disease	C10.228.140.163.100.435.825.300.300.249; C16.320.565.189.435.825.300.300.249; C16.320.565.398.641.803.350.300.700; C16.320.565.595.554.825.300.300.800; C18.452.132.100.435.825.300.300.249; C18.452.584.563.641.803.350.300.700; C18.452.648.189.435.825.300.300.249; C18.452.648.398.641.803.350.300.700; C18.452.648.595.554.825.300.300.800
D013167	Spondylitis, Ankylosing	C05.116.900.853.625.800.744.500; C05.550.069.340.500; C05.550.114.865.800.744.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00133315	PHASE4	COMPLETED	TNFalfa Blocking Treatment of Spondylarthropathies
NCT00247962	PHASE4	COMPLETED	Study Evaluating Etanercept and Sulphasalazine in Ankylosing Spondylitis
NCT00410046	PHASE4	COMPLETED	Extension Study Evaluating Etanercept in Ankylosing Spondylitis
NCT00420238	PHASE4	COMPLETED	Study Evaluating Etanercept for the Treatment of Active, Severe, and Advanced Axial Ankylosing Spondylitis
NCT00432432	PHASE4	COMPLETED	Combination Methotrexate and Infliximab
NCT00444340	PHASE4	COMPLETED	An Open-Label Multicentre Long-Term Extension Study of Etanercept for Ankylosing Spondylitis
NCT00458185	PHASE4	COMPLETED	Study Evaluating Etanercept in Patients With Ankylosing Spondylitis
NCT00507403	PHASE4	COMPLETED	Infliximab and Methotrexate in Ankylosing Spondylitis
NCT00647517	PHASE4	COMPLETED	Tramadol/Acetaminophen(Ultracet) AS add-on Therapy in the Treatment of Patients With Ankylosing Spondylitis
NCT00715091	PHASE4	COMPLETED	Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on RAdiographic Damage in Ankylosing Spondylitis
NCT00873730	PHASE4	COMPLETED	Study Evaluating Etanercept in Subjects With Ankylosing Spondylitis in Spain
NCT00910273	PHASE4	TERMINATED	Effects of Etanercept on the Heart, Veins and Thickness of Certain Major Arteries In Ankylosing Spondylitis Patients
NCT00953979	PHASE4	COMPLETED	Efficacy and Safety of Kunxian Capsule in Treatment Patients With Early Ankylosing Spondylitis
NCT01148901	PHASE4	WITHDRAWN	Effectiveness and Safety of Early Treatment With Infliximab for Hip Arthritis Associated With Ankylosing Spondylitis (AS) (P06451)
NCT01212653	PHASE4	COMPLETED	Effect of Anti-TNF (Alpha) Treatment on Vascular Stiffness in Ankylosing Spondylitis (AS)
NCT01422564	PHASE4	TERMINATED	Metal on Metal Versus Metal on Highly Crossed Linked Polyethylene Sytem
NCT01517620	PHASE4	COMPLETED	Total Glucosides Paeony Capsules in Maintaining Clinical Remission in Patients With Ankylosing Spondylitis Which Achieve Clinical Remission After Anti-TNF Therapy
NCT01668004	PHASE4	COMPLETED	The Incidence of Extra-Articular Manifestations in Participants With Ankylosing Spondylitis Treated With Golimumab (MK-8259-012)
NCT01895764	PHASE4	COMPLETED	Effect of the Combination of Methotrexate and Adalimumab on Reduction of Immunization in Ankylosing Spondylitis (COMARIS)
NCT01934933	PHASE4	COMPLETED	Etanercept and Celecoxib Alone/Combined Treatment in Effectiveness and Safety of Active Ankylosing Spondylitis
NCT02132234	PHASE4	UNKNOWN	Effects of Biological Treatment on Blood Pressure and Endothelial Function in Patients With Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis
NCT02313727	PHASE4	UNKNOWN	Combined Treatment With TNF Inhibitor and Pamidronate in AS Patients: Effect on the Radiographic Progression
NCT02489760	PHASE4	UNKNOWN	Etanercept Versus Adalimumab in the Treatment of Patients With Ankylosing Spondylitis. A Switch Study
NCT02492217	PHASE4	COMPLETED	Biomarkers Identification of Anti-tumor Necrosis Factor (TNF) α Agent’s Efficacy in Ankylosing Spondylitis Patients
NCT02528201	PHASE4	COMPLETED	A Study Of Celecoxib Versus Diclofenac In Patients With Ankylosing Spondylitis
NCT02638896	PHASE4	UNKNOWN	Dose Reduction of Etanercept in Patients With Ankylosing Spondylitis
NCT02758782	PHASE4	COMPLETED	NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis
NCT02763046	PHASE4	COMPLETED	Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis
NCT03350815	PHASE4	COMPLETED	Study Estimating the Clinical Difference Between 300 mg and 150 mg of Secukinumab Following Dose Escalation to 300 mg in Patients With Ankylosing Spondylitis
NCT03411798	PHASE4	COMPLETED	Sequential Application of Yisaipu® and DMARDs in Treating Mild-to-Moderate AS
NCT03473665	PHASE4	TERMINATED	Non-Steroidal Anti-inflammatory Drugs in Axial Spondyloarthritis
NCT03639740	PHASE4	UNKNOWN	Treat-to-target With Secukinumab in Axial Spondyloarthritis
NCT03800797	PHASE4	COMPLETED	Efficacy and Safety of Loxoprofen Hydrogel Patch in Patients With Ankylosing Spondylitis
NCT03932006	PHASE4	UNKNOWN	A Multicenter，Double-Blind and Randomized Controlled Trial of Fengshigutong Capsule in the Treatment of Ankylosing Spondylitis
NCT04077957	PHASE4	UNKNOWN	Treat-to-target Strategy in Ankylosing Spondylitis Using Etanercept and Conventional Synthetic DMARDs
NCT04885751	PHASE4	UNKNOWN	Compare the Effect of Eupatilin and Rebamipide on the Prevention of Gastroenteropathy
NCT04934059	PHASE4	UNKNOWN	Efficacy and Safety of Yuxuebi Tablet in Treating Night Pain of Ankylosing Spondylitis (AS).
NCT05164198	PHASE4	UNKNOWN	REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)
NCT05303285	PHASE4	RECRUITING	A Study Evaluating the Efficacy of Secukinumab 300mg in Chinese Adults With Active Ankylosing Spondylitis
NCT05527444	PHASE4	UNKNOWN	The Clinical Efficacy and the Changes of Immune Cells Subsets With Bioagents in Ankylosing Spondylitis Patients