ANKS4B

Summary

ANKS4B (ankyrin repeat and sterile alpha motif domain containing 4B, HGNC:26795) is a protein-coding gene on chromosome 16p12.2, encoding Ankyrin repeat and SAM domain-containing protein 4B (Q8N8V4). As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length.

Involved in brush border assembly; protein localization to microvillus; and protein-containing complex assembly. Located in brush border and microvillus.

Source: NCBI Gene 257629 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_145865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26795
Approved symbol	ANKS4B
Name	ankyrin repeat and sterile alpha motif domain containing 4B
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38819, HARP
Ensembl gene	ENSG00000175311
Ensembl biotype	protein_coding
OMIM	609901
Entrez	257629

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000311620

RefSeq mRNA: 1 — MANE Select: NM_145865 NM_145865

CCDS: CCDS42130

Canonical transcript exons

ENST00000311620 — 2 exons

Exon	Start	End
ENSE00001189612	21233699	21233901
ENSE00001234462	21249731	21253850

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 87.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6728 / max 140.5843, expressed in 80 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153100	0.6728	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	87.80	gold quality
duodenum	UBERON:0002114	86.54	gold quality
rectum	UBERON:0001052	84.09	gold quality
liver	UBERON:0002107	82.71	gold quality
right lobe of liver	UBERON:0001114	80.01	gold quality
small intestine	UBERON:0002108	75.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.90	gold quality
transverse colon	UBERON:0001157	73.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.79	silver quality
adult mammalian kidney	UBERON:0000082	73.74	gold quality
gall bladder	UBERON:0002110	70.11	gold quality
colonic epithelium	UBERON:0000397	69.91	gold quality
kidney	UBERON:0002113	69.00	gold quality
intestine	UBERON:0000160	65.20	gold quality
islet of Langerhans	UBERON:0000006	63.66	gold quality
vermiform appendix	UBERON:0001154	61.57	gold quality
colon	UBERON:0001155	60.64	gold quality
cortex of kidney	UBERON:0001225	56.28	gold quality
sural nerve	UBERON:0015488	55.45	gold quality
cerebellum	UBERON:0002037	53.26	gold quality
cerebellar cortex	UBERON:0002129	53.24	gold quality
cerebellar hemisphere	UBERON:0002245	53.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.40	gold quality
smooth muscle tissue	UBERON:0001135	51.66	gold quality
pancreas	UBERON:0001264	49.39	gold quality
metanephros cortex	UBERON:0010533	48.17	gold quality
stomach	UBERON:0000945	44.66	gold quality
muscle tissue	UBERON:0002385	43.62	gold quality
body of stomach	UBERON:0001161	43.50	gold quality
mucosa of stomach	UBERON:0001199	42.76	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, HNF4A

miRNA regulators (miRDB)

68 targeting ANKS4B, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 3)

• ankyrin repeat and sterile alpha motif domain containing 4B (ANKS4B) localizes to the tips of adherent brush border microvilli and is essential for intermicrovillar adhesion (PMID:26812018)
• Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation. (PMID:31644917)
• A cryptic sequence targets the adhesion complex scaffold ANKS4B to apical microvilli to promote enterocyte brush border assembly. (PMID:32636301)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	anks4b	ENSDARG00000036846
mus_musculus	Anks4b	ENSMUSG00000030909
rattus_norvegicus	Anks4b	ENSRNOG00000046181
drosophila_melanogaster	Sans	FBGN0033785

Paralogs (1): USH1G (ENSG00000182040)

Protein

Protein identifiers

Ankyrin repeat and SAM domain-containing protein 4B — Q8N8V4 (reviewed: Q8N8V4)

Alternative names: Harmonin-interacting ankyrin repeat-containing protein

All UniProt accessions (1): Q8N8V4

UniProt curated annotations — full annotation on UniProt →

Function. As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. Plays a role in assembly of the complex. May play a role in cellular response to endoplasmic reticulum stress.

Subunit / interactions. Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5. Interacts with USH1C; the interaction is direct and is required for ANKS4B localization to the tip of microvilli. Interacts with MYO7B; the interaction is direct. May interact with HSPA5.

Subcellular location. Cell projection. Microvillus.

Tissue specificity. Expressed in kidney and small intestine.

RefSeq proteins (1): NP_665872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037601	ANKS4B_SAM	Domain

Pfam: PF00536, PF12796

UniProt features (16 total): region of interest 4, repeat 3, compositionally biased region 2, mutagenesis site 2, chain 1, short sequence motif 1, modified residue 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8V4-F1	70.57	0.42

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): 283

Mutagenesis-validated functional residues (2):

Position	Phenotype
48	decreased localization to microvilli.
417	decreased interaction with ush1c.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOCC_APICAL_PART_OF_CELL, chr16p12, GOCC_MICROVILLUS, GOCC_CLUSTER_OF_ACTIN_BASED_CELL_PROJECTIONS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ACTIN_BASED_CELL_PROJECTION, GOCC_ORGANELLE_SUBCOMPARTMENT, GOCC_BRUSH_BORDER, BAKKER_FOXO3_TARGETS_DN, SERVITJA_ISLET_HNF1A_TARGETS_DN, GOBP_BRUSH_BORDER_ASSEMBLY, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP, HHEX_TARGET_GENES

GO Biological Process (5): cell differentiation (GO:0030154), response to endoplasmic reticulum stress (GO:0034976), protein-containing complex assembly (GO:0065003), protein localization to microvillus (GO:1904106), brush border assembly (GO:1904970)

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

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), microvillus (GO:0005902), brush border (GO:0005903), cell projection (GO:0042995), plasma membrane bounded cell projection (GO:0120025)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular component assembly	2
cellular developmental process	1
cellular response to stress	1
protein-containing complex organization	1
protein localization to actin cytoskeleton	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
actin filament bundle	1
actin-based cell projection	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
cellular anatomical structure	1
cell projection	1
plasma membrane region	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKS4B	MYO7B	Q6PIF6	899
ANKS4B	E9PNW1	E9PNW1	887
ANKS4B	CDHR5	Q9HBB8	802
ANKS4B	CDHR2	Q9BYE9	790
ANKS4B	PLA2G12B	Q9BX93	539
ANKS4B	ABHD15	Q6UXT9	526
ANKS4B	N4BP2L1	Q5TBK1	507
ANKS4B	ZNF732	B4DXR9	505
ANKS4B	ZSWIM3	Q96MP5	484
ANKS4B	SLC35D1	Q9NTN3	434
ANKS4B	CDH23	Q9H251	430
ANKS4B	LDLRAD1	Q5T700	426
ANKS4B	SLC7A14	Q8TBB6	406
ANKS4B	TM4SF4	P48230	387
ANKS4B	MYO7A	P78427	383

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ANKS4B	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.620
LRRK2	ANKS4B	psi-mi:“MI:0407”(direct interaction)	0.620
ANKS4B	USH1C	psi-mi:“MI:0915”(physical association)	0.560
ANKS4B	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
	ANKS4B	psi-mi:“MI:0407”(direct interaction)	0.440
ANKS4B	PLEC	psi-mi:“MI:0915”(physical association)	0.400
ANKS4B	MPP7	psi-mi:“MI:0914”(association)	0.350
ANKS4B	USH1C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): ANKS4B (Biochemical Activity), ANKS4B (Reconstituted Complex), ANKS4B (Reconstituted Complex), ANKS4B (Two-hybrid), ANKS4B (Proximity Label-MS), BANP (Affinity Capture-MS), USH1C (Affinity Capture-MS), MPP7 (Affinity Capture-MS), ANKS4B (Cross-Linking-MS (XL-MS)), ATP6V1E1 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A0JPH7, A1A5Q0, B0R034, E1BTG2, E1C065, E1C760, F1MUG2, F7AEX0, G3XA57, O60308, P30306, P48966, Q02225, Q0IID7, Q0VBD2, Q14B46, Q28E45, Q28FA8, Q3UHZ5, Q4KM37, Q5EAW4, Q5FWH3, Q5JTW2, Q5RHY1, Q5XGX5, Q60949, Q6GQN0, Q6INA9, Q6NTY8, Q6NU40, Q6P5Q4, Q7L590, Q80U87, Q8BN58, Q8BXR9, Q8BZN6, Q8C5W4, Q8GT06, Q8K3X6, Q8N8V4

Diamond homologs: O94830, Q495M9, Q6NZC7, Q80T11, Q80Y98, Q80YA3, Q8K3X6, Q8N8V4, Q9Y6Y8, O14593, Q3KP44, Q8BLD6, Q9Z205, P0C0T2, Q24009, Q5M9H0, Q5U4T7, Q5XJ13, Q68DC2, Q6GQX6, Q6ZW76, Q99MQ1, Q9CZK6, Q9H694, Q9IA00, O00562, O35954, P43125, Q12204, Q3UHE1, Q5U2N3, Q6ZPQ6, Q9BZ71, Q9BZ72

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	ANKS4B	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

197 predictions. Top by Δscore:

Variant	Effect	Δscore
16:21233898:GAGG:G	donor_gain	1.0000
16:21233900:GG:G	donor_gain	1.0000
16:21233901:GG:G	donor_gain	1.0000
16:21233902:G:GA	donor_loss	1.0000
16:21233902:G:GG	donor_gain	1.0000
16:21233903:T:TC	donor_loss	1.0000
16:21249727:CTA:C	acceptor_loss	1.0000
16:21249728:TA:T	acceptor_loss	1.0000
16:21249729:A:AG	acceptor_gain	1.0000
16:21249729:AGAG:A	acceptor_gain	1.0000
16:21249729:AGAGG:A	acceptor_gain	1.0000
16:21249730:G:GG	acceptor_gain	1.0000
16:21249730:GA:G	acceptor_gain	1.0000
16:21249730:GAGG:G	acceptor_gain	1.0000
16:21249730:GAGGG:G	acceptor_gain	1.0000
16:21233899:AGG:A	donor_gain	0.9900
16:21233900:GGG:G	donor_gain	0.9900
16:21237577:G:GT	donor_gain	0.9900
16:21237582:G:T	donor_gain	0.9900
16:21249728:TAGAG:T	acceptor_gain	0.9900
16:21249727:CTAGA:C	acceptor_gain	0.9800
16:21233899:AGGGT:A	donor_gain	0.9700
16:21233900:GGGT:G	donor_gain	0.9700
16:21233901:GGT:G	donor_gain	0.9700
16:21233902:GT:G	donor_gain	0.9700
16:21234166:G:T	donor_gain	0.9700
16:21237586:G:GT	donor_gain	0.9700
16:21249726:TCTAG:T	acceptor_gain	0.9700
16:21249727:CTAG:C	acceptor_gain	0.9700
16:21249728:TAG:T	acceptor_gain	0.9700

AlphaMissense

2773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:21233841:C:A	P35H	0.996
16:21233763:C:A	A9D	0.995
16:21250711:T:C	L382P	0.993
16:21233841:C:G	P35R	0.992
16:21233856:C:A	A40D	0.992
16:21249784:C:A	A73D	0.992
16:21249880:C:A	A105D	0.992
16:21233880:T:C	L48P	0.991
16:21249751:A:T	D62V	0.991
16:21249781:C:A	A72E	0.991
16:21249760:G:T	G65V	0.989
16:21233787:T:C	L17P	0.988
16:21233853:C:A	A39E	0.988
16:21249783:G:C	A73P	0.988
16:21249769:C:G	P68R	0.987
16:21249808:T:A	V81D	0.987
16:21249817:T:C	L84P	0.987
16:21233795:G:C	A20P	0.986
16:21233852:G:C	A39P	0.986
16:21233855:G:C	A40P	0.986
16:21233865:G:T	G43V	0.986
16:21233796:C:A	A20D	0.985
16:21233864:G:T	G43W	0.985
16:21249916:T:C	L117P	0.985
16:21249769:C:A	P68H	0.984
16:21249772:T:C	L69P	0.984
16:21249879:G:C	A105P	0.983
16:21249751:A:C	D62A	0.982
16:21249752:C:A	D62E	0.982
16:21249752:C:G	D62E	0.982

dbSNP variants (sampled 300 via entrez): RS1000115582 (16:21249582 G>A), RS1000584447 (16:21235720 C>G), RS1000873649 (16:21236966 T>C), RS1000928051 (16:21248286 G>A,C,T), RS1000928439 (16:21242355 T>C), RS1000959339 (16:21248622 C>T), RS1001519679 (16:21244199 T>C), RS1001550812 (16:21242859 A>C), RS1001671435 (16:21250690 T>C), RS1001707997 (16:21237082 G>A), RS1001997361 (16:21241760 T>C), RS1002065181 (16:21243236 A>C,G), RS1002141285 (16:21238494 TATAC>T), RS1002284303 (16:21241549 T>A), RS1002451483 (16:21247541 G>A)

Disease associations

OMIM: gene MIM:609901 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003226_4	Pelvic organ prolapse	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
propionaldehyde	decreases expression	1
beta-lapachone	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression	1
Aldehydes	decreases expression	1
Cisplatin	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Silver	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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