ANKRD13D

Summary

ANKRD13D (ankyrin repeat domain 13D, HGNC:27880) is a protein-coding gene on chromosome 11q13.2, encoding Ankyrin repeat domain-containing protein 13D (Q6ZTN6). Ubiquitin-binding protein that specifically recognizes and binds ‘Lys-63’-linked ubiquitin.

The protein encoded by this gene is a member of the ankyrin repeat domain (ANKRD) 13 family, which currently consists of four proteins containing ubiquitin-interacting motifs. These proteins are integral membrane proteins that bind specifically to Lys-63-linked ubiquitin chains on membrane-bound proteins, targeting those proteins for rapid internalization.

Source: NCBI Gene 338692 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_207354

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27880
Approved symbol	ANKRD13D
Name	ankyrin repeat domain 13D
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172932
Ensembl biotype	protein_coding
OMIM	615126
Entrez	338692

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 retained_intron, 6 protein_coding, 2 nonsense_mediated_decay

ENST00000308440, ENST00000447274, ENST00000504186, ENST00000504236, ENST00000504729, ENST00000506119, ENST00000506531, ENST00000507915, ENST00000508417, ENST00000508422, ENST00000511455, ENST00000512101, ENST00000512231, ENST00000513460, ENST00000513750, ENST00000514779, ENST00000515828, ENST00000908429, ENST00000908430, ENST00000920434, ENST00000920435

RefSeq mRNA: 2 — MANE Select: NM_207354 NM_001347901, NM_207354

CCDS: CCDS31616

Canonical transcript exons

ENST00000511455 — 15 exons

Exon	Start	End
ENSE00002307747	67289303	67289550
ENSE00003473106	67291991	67292180
ENSE00003479781	67301488	67301651
ENSE00003489800	67291603	67291746
ENSE00003566208	67301282	67301398
ENSE00003580258	67299993	67300123
ENSE00003627908	67291476	67291521
ENSE00003634894	67299058	67299124
ENSE00003640541	67299530	67299611
ENSE00003643775	67290322	67290446
ENSE00003651490	67301732	67301823
ENSE00003651689	67300990	67301147
ENSE00003659683	67290078	67290213
ENSE00003674236	67302119	67302484
ENSE00003684181	67299827	67299888

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8686 / max 79.8248, expressed in 1760 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115431	5.5692	1709
115432	1.9517	1215
115430	0.3477	163

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.74	gold quality
pancreatic ductal cell	CL:0002079	98.29	gold quality
lower esophagus mucosa	UBERON:0035834	98.09	gold quality
right uterine tube	UBERON:0001302	96.81	gold quality
adenohypophysis	UBERON:0002196	96.80	gold quality
spleen	UBERON:0002106	96.55	gold quality
monocyte	CL:0000576	96.38	gold quality
leukocyte	CL:0000738	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.92	gold quality
pituitary gland	UBERON:0000007	95.85	gold quality
cerebellar hemisphere	UBERON:0002245	95.76	gold quality
cerebellar cortex	UBERON:0002129	95.63	gold quality
right frontal lobe	UBERON:0002810	95.25	gold quality
skin of leg	UBERON:0001511	95.18	gold quality
skin of abdomen	UBERON:0001416	95.14	gold quality
anterior cingulate cortex	UBERON:0009835	94.84	gold quality
minor salivary gland	UBERON:0001830	94.82	gold quality
endocervix	UBERON:0000458	94.78	gold quality
esophagus mucosa	UBERON:0002469	94.78	gold quality
vermiform appendix	UBERON:0001154	94.60	gold quality
ectocervix	UBERON:0012249	94.54	gold quality
blood	UBERON:0000178	94.41	gold quality
cerebellum	UBERON:0002037	94.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.20	gold quality
lymph node	UBERON:0000029	94.15	gold quality
metanephros cortex	UBERON:0010533	93.92	gold quality
tibial nerve	UBERON:0001323	93.86	gold quality
hypothalamus	UBERON:0001898	93.80	gold quality
left uterine tube	UBERON:0001303	93.78	gold quality
mucosa of stomach	UBERON:0001199	93.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.12
E-MTAB-7303	no	66.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting ANKRD13D, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-874-5P	96.93	63.92	1014

Literature-anchored findings (GeneRIF, showing 2)

• overexpression of wild-type as well as truncated-mutant Ankrd 13A, 13B and 13D proteins strongly inhibited rapid endocytosis of ubiquitinated EGFR from the surface in EGF-treated cells (PMID:22298428)
• Identification of ANKRD13D as a potential target in renal cell carcinomas. (PMID:38449090)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd13d	ENSDARG00000098140
mus_musculus	Ankrd13d	ENSMUSG00000005986
rattus_norvegicus	Ankrd13d	ENSRNOG00000028247
drosophila_melanogaster	CG15118	FBGN0034418
caenorhabditis_elegans		WBGENE00015978

Paralogs (3): ANKRD13A (ENSG00000076513), ANKRD13C (ENSG00000118454), ANKRD13B (ENSG00000198720)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 13D — Q6ZTN6 (reviewed: Q6ZTN6)

All UniProt accessions (4): Q6ZTN6, A0A087WWH4, A0A6E1W3F4, A0A6E1YH78

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-binding protein that specifically recognizes and binds ‘Lys-63’-linked ubiquitin. Does not bind ‘Lys-48’-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane.

Subunit / interactions. Interacts with EGFR (ubiquitinated); the interaction is direct and may regulate EGFR internalization.

Subcellular location. Cell membrane. Late endosome.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZTN6-3	3	yes
Q6ZTN6-1	1
Q6ZTN6-2	2

RefSeq proteins (2): NP_001334830, NP_997237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR003903	UIM_dom	Conserved_site
IPR021832	ANKRD13	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR055285	ANKRD13_C	Domain

Pfam: PF11904, PF12796

UniProt features (23 total): sequence conflict 5, compositionally biased region 4, domain 4, repeat 2, modified residue 2, splice variant 2, region of interest 2, chain 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7RMA	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZTN6-F1	73.38	0.21

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 (2): 552, 556

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, chr11q13, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION, GOBP_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, TGCTGAY_UNKNOWN, GOBP_RECEPTOR_INTERNALIZATION, GOBP_REGULATION_OF_ENDOCYTOSIS, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, RFX1_02, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN

GO Biological Process (1): negative regulation of receptor internalization (GO:0002091)

GO Molecular Function (2): ubiquitin-modified protein reader activity (GO:0140036), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), late endosome (GO:0005770), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), endosome (GO:0005768), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of receptor internalization	1
receptor internalization	1
negative regulation of receptor-mediated endocytosis	1
ubiquitin-like protein reader activity	1
binding	1
intracellular anatomical structure	1
endosome	1
membrane	1
cell periphery	1
cytoplasm	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

451 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD13D	LRRC73	Q5JTD7	665
ANKRD13D	TEPSIN	Q96N21	626
ANKRD13D	VSIG10	Q8N0Z9	559
ANKRD13D	POLR3H	Q9Y535	473
ANKRD13D	FAM222A	Q5U5X8	465
ANKRD13D	TBCCD1	Q9NVR7	458
ANKRD13D	ENKD1	Q9H0I2	446
ANKRD13D	DOCK3	Q8IZD9	440
ANKRD13D	NPRL2	Q8WTW4	436
ANKRD13D	PFDN2	Q9UHV9	422
ANKRD13D	FAM220A	Q7Z4H9	419
ANKRD13D	KRTAP5-10	Q6L8G5	379
ANKRD13D	C1orf162	Q8NEQ5	373
ANKRD13D	TANC2	Q9HCD6	368
ANKRD13D	SLIT1	O75093	360

IntAct

86 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
ANKRD13D	ENTREP1	psi-mi:“MI:0915”(physical association)	0.660
CSNK1G3	CSNK1G2	psi-mi:“MI:0914”(association)	0.640
MS4A10	NEDD4	psi-mi:“MI:0914”(association)	0.590
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
TNFAIP3	UBB	psi-mi:“MI:0914”(association)	0.530
TMEM255A	WWP2	psi-mi:“MI:0914”(association)	0.530
FKBP11	ANKRD13D	psi-mi:“MI:0914”(association)	0.530
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.530
IZUMO1	ADCY3	psi-mi:“MI:0914”(association)	0.530
ZNRF1	NMT2	psi-mi:“MI:0914”(association)	0.530
PI4K2A	GABARAP	psi-mi:“MI:0914”(association)	0.530
ENTREP3	NEDD4	psi-mi:“MI:0914”(association)	0.530
FAM78B	RPS27A	psi-mi:“MI:0914”(association)	0.530
TRIM10	WIZ	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
ANKRD13D	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ERGIC3	TMEM223	psi-mi:“MI:0914”(association)	0.350
FAM189B	KLRG2	psi-mi:“MI:0914”(association)	0.350
IZUMO1	CNOT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): UBC (Reconstituted Complex), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), VCP (Affinity Capture-MS), VCP (Affinity Capture-Western), ANKRD13D (Affinity Capture-Western), ANKRD13D (Biochemical Activity), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8FDW4, A4QP73, A4UMC5, B4NYQ2, B5X0I6, C4R2L0, D4A6D7, O09012, O70525, O74711, P33292, P50542, Q01495, Q1RMV0, Q29RR5, Q2M2R8, Q2TXF0, Q54MD1, Q5AV00, Q5F259, Q5R4F4, Q5U2Y6, Q5ZMQ9, Q6BM14, Q6CT48, Q6DI35, Q6DKK2, Q6FM42, Q6K687, Q6PD24, Q6ZTN6, Q752X0, Q80UP5, Q86YJ7, Q8C437, Q8CC21, Q8IYB4, Q8IZ07, Q8L611, Q920N5

Diamond homologs: A4II29, Q28C34, Q3UX43, Q5F259, Q5U5A6, Q6NRD0, Q6PD24, Q6ZTN6, Q7T3Y0, Q7Z6K4, Q7ZUV0, Q7ZYD9, Q80UP5, Q86WC6, Q86YJ7, Q8IZ07, Q8N6S4, Q91ZA8, Q9D119, Q9TXQ1, Q3V096, P42570, Q0VC93, Q28FJ2, Q4JHE0, Q569N2, Q7Z713

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	ANKRD13D	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of PTEN stability and activity	5	13.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2948 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67289548:CAGGT:C	donor_loss	1.0000
11:67289550:GGT:G	donor_loss	1.0000
11:67289551:G:C	donor_loss	1.0000
11:67290320:A:AG	acceptor_gain	1.0000
11:67290321:G:GG	acceptor_gain	1.0000
11:67291601:A:AG	acceptor_gain	1.0000
11:67291602:G:GA	acceptor_gain	1.0000
11:67291602:GT:G	acceptor_gain	1.0000
11:67291602:GTGC:G	acceptor_gain	1.0000
11:67291745:GG:G	donor_gain	1.0000
11:67291746:GG:G	donor_gain	1.0000
11:67291979:A:AG	acceptor_gain	1.0000
11:67291979:ACC:A	acceptor_gain	1.0000
11:67291979:ACCG:A	acceptor_gain	1.0000
11:67291980:C:G	acceptor_gain	1.0000
11:67291981:C:CA	acceptor_gain	1.0000
11:67291982:G:A	acceptor_gain	1.0000
11:67291985:C:A	acceptor_gain	1.0000
11:67292162:G:GG	donor_gain	1.0000
11:67292178:GAG:G	donor_gain	1.0000
11:67299130:A:T	donor_gain	1.0000
11:67299607:CAAAG:C	donor_loss	1.0000
11:67299608:AAAGG:A	donor_loss	1.0000
11:67299609:AAGGT:A	donor_loss	1.0000
11:67299610:AGGT:A	donor_loss	1.0000
11:67299611:GGTAA:G	donor_loss	1.0000
11:67299612:GT:G	donor_loss	1.0000
11:67299613:T:A	donor_loss	1.0000
11:67299825:A:AG	acceptor_gain	1.0000
11:67299826:G:GG	acceptor_gain	1.0000

AlphaMissense

3942 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67291503:T:A	W40R	1.000
11:67291503:T:C	W40R	1.000
11:67291505:G:C	W40C	1.000
11:67291505:G:T	W40C	1.000
11:67291509:T:C	F42L	1.000
11:67291510:T:C	F42S	1.000
11:67291511:C:A	F42L	1.000
11:67291511:C:G	F42L	1.000
11:67291515:A:C	S44R	1.000
11:67291517:C:A	S44R	1.000
11:67291517:C:G	S44R	1.000
11:67291652:G:C	K62N	1.000
11:67291652:G:T	K62N	1.000
11:67291725:A:C	S87R	1.000
11:67291727:C:A	S87R	1.000
11:67291727:C:G	S87R	1.000
11:67299540:C:A	A183D	1.000
11:67301004:T:C	L276P	1.000
11:67301010:T:C	L278P	1.000
11:67301097:T:C	L307P	1.000
11:67301132:T:C	F319L	1.000
11:67301134:C:A	F319L	1.000
11:67301134:C:G	F319L	1.000
11:67301136:C:A	P320H	1.000
11:67301285:T:C	I325T	1.000
11:67301309:C:A	A333D	1.000
11:67291485:T:C	F34L	0.999
11:67291487:C:A	F34L	0.999
11:67291487:C:G	F34L	0.999
11:67291492:T:A	V36D	0.999

dbSNP variants (sampled 300 via entrez): RS1000210030 (11:67290219 G>C,T), RS1000217417 (11:67293245 G>C), RS1000262406 (11:67290492 C>T), RS1000378333 (11:67301660 T>C), RS1000515371 (11:67289571 C>T), RS1000991552 (11:67300322 T>G), RS1001274048 (11:67294813 A>G), RS1001316774 (11:67296482 G>A), RS1001383572 (11:67289046 G>A,T), RS1001535859 (11:67291049 A>G), RS1002217273 (11:67290842 C>G,T), RS1002225258 (11:67301078 A>G), RS1002478129 (11:67300674 G>A), RS1002575438 (11:67300598 C>G,T), RS1002813068 (11:67300400 C>A,T)

Disease associations

OMIM: gene MIM:615126 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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