ANKRD17

Summary

ANKRD17 (ankyrin repeat domain 17, HGNC:23575) is a protein-coding gene on chromosome 4q13.3, encoding Ankyrin repeat domain-containing protein 17 (O75179). Could play pivotal roles in cell cycle and DNA regulation. It is a selective cancer dependency (DepMap: 13.3% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene belongs to the family of ankyrin repeat-containing proteins, and contains two distinct arrays of ankyrin repeats in its amino-terminal region, one with 15 ankyrin repeats, and the other with 10 ankyrin repeats. It also contains a nuclear export signal, nuclear localization signal, and a cyclin-binding RXL motif. Localization of this protein to the nucleus has been shown experimentally, and interactions between this protein and cyclin-dependent kinase 2 have been observed. It has been suggested that this protein plays a role in both DNA replication and in both anti-viral and anti-bacterial innate immune pathways. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 26057 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 584 total — 18 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 35
• Cancer dependency (DepMap): dependent in 13.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_032217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23575
Approved symbol	ANKRD17
Name	ankyrin repeat domain 17
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	GTAR, KIAA0697, FLJ22206, NY-BR-16, MASK2
Ensembl gene	ENSG00000132466
Ensembl biotype	protein_coding
OMIM	615929
Entrez	26057

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000330838, ENST00000358602, ENST00000509867, ENST00000510127, ENST00000513908, ENST00000514252, ENST00000558247, ENST00000559367, ENST00000560507, ENST00000561029, ENST00000914559, ENST00000914560, ENST00000914561, ENST00000914562

RefSeq mRNA: 4 — MANE Select: NM_032217 NM_001286771, NM_015574, NM_032217, NM_198889

CCDS: CCDS34003, CCDS34004, CCDS68721

Canonical transcript exons

ENST00000358602 — 34 exons

Exon	Start	End
ENSE00000904406	73153880	73154113
ENSE00000904407	73155631	73155778
ENSE00000904408	73156019	73156166
ENSE00001024832	73147241	73147432
ENSE00001605787	73097117	73097272
ENSE00001605872	73090667	73092300
ENSE00001723277	73085249	73085446
ENSE00001726219	73094079	73094228
ENSE00002028090	73258276	73258798
ENSE00002051724	73073376	73076290
ENSE00002454077	73077355	73077533
ENSE00002531739	73076940	73077104
ENSE00003463665	73078642	73078890
ENSE00003478324	73118688	73118850
ENSE00003487096	73098073	73098520
ENSE00003506664	73125201	73125312
ENSE00003515859	73144745	73144832
ENSE00003518065	73139531	73140283
ENSE00003552930	73120881	73121094
ENSE00003588381	73142640	73142767
ENSE00003600915	73141741	73141843
ENSE00003600978	73146764	73146873
ENSE00003601623	73142242	73142385
ENSE00003605000	73121617	73121759
ENSE00003620284	73148813	73149050
ENSE00003627891	73124913	73125058
ENSE00003630833	73120162	73120337
ENSE00003641226	73102376	73102547
ENSE00003649296	73135117	73135265
ENSE00003656052	73113792	73113908
ENSE00003669919	73177380	73177533
ENSE00003670201	73151430	73151524
ENSE00003672891	73115821	73115916
ENSE00003673262	73161192	73161348

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.3635 / max 645.9126, expressed in 1825 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52478	14.8843	1796
52479	9.0918	1757
52480	5.4305	1612
52474	4.5184	1405
52475	1.9583	931
52466	0.6794	377
52477	0.3232	142
52467	0.2912	86
52473	0.1865	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.97	gold quality
sural nerve	UBERON:0015488	98.17	gold quality
visceral pleura	UBERON:0002401	97.50	gold quality
parietal pleura	UBERON:0002400	96.92	gold quality
middle temporal gyrus	UBERON:0002771	96.89	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.22	gold quality
medial globus pallidus	UBERON:0002477	96.17	gold quality
pleura	UBERON:0000977	96.15	gold quality
cardia of stomach	UBERON:0001162	95.96	gold quality
globus pallidus	UBERON:0001875	95.76	gold quality
pylorus	UBERON:0001166	95.73	gold quality
pigmented layer of retina	UBERON:0001782	95.53	gold quality
postcentral gyrus	UBERON:0002581	95.53	gold quality
renal medulla	UBERON:0000362	95.50	gold quality
substantia nigra pars compacta	UBERON:0001965	95.47	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.47	gold quality
lateral globus pallidus	UBERON:0002476	95.35	gold quality
parietal lobe	UBERON:0001872	95.22	gold quality
tendon of biceps brachii	UBERON:0008188	95.18	gold quality
nipple	UBERON:0002030	95.05	gold quality
tibia	UBERON:0000979	94.97	gold quality
superior frontal gyrus	UBERON:0002661	94.85	gold quality
epithelium of nasopharynx	UBERON:0001951	94.80	gold quality
dorsal root ganglion	UBERON:0000044	94.77	gold quality
entorhinal cortex	UBERON:0002728	94.73	gold quality
colonic epithelium	UBERON:0000397	94.61	gold quality
adrenal tissue	UBERON:0018303	94.45	gold quality
primary visual cortex	UBERON:0002436	94.31	gold quality
tendon	UBERON:0000043	94.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

211 targeting ANKRD17, 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-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
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-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 13.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• there are overlapping reading frames in the mouse and human genes for 4E-BP3 and MASK (PMID:14557257)
• The results indicated that ankrd17 is a positive regulator of the RIG-I signaling pathway. Ankrd17 enhanced the interaction of RIG-I and MDA5 with VISA; the ankyrin repeat domain of ankrd17 is required for its interaction with RIG-I. (PMID:22328336)
• A novel function for Ankrd17 in Nod1 and Nod2 mediated anti-bacterial innate immune pathways. (PMID:23711367)
• Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism. (PMID:33909992)
• CircANKRD17 promotes glycolysis by inhibiting miR-143 in breast cancer cells. (PMID:37812578)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ankrd17	ENSMUSG00000055204
rattus_norvegicus	Ankrd17	ENSRNOG00000002940

Paralogs (1): ANKHD1 (ENSG00000131503)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 17 — O75179 (reviewed: O75179)

Alternative names: Gene trap ankyrin repeat protein, Serologically defined breast cancer antigen NY-BR-16

All UniProt accessions (3): O75179, H0YLQ3, H0YM23

UniProt curated annotations — full annotation on UniProt →

Function. Could play pivotal roles in cell cycle and DNA regulation. Involved in innate immune defense against viruse by positively regulating the viral dsRNA receptors DDX58 and IFIH1 signaling pathways. Involves in NOD2- and NOD1-mediated responses to bacteria suggesting a role in innate antibacterial immune pathways too. Target of enterovirus 71 which is the major etiological agent of HFMD (hand, foot and mouth disease). Could play a central role for the formation and/or maintenance of the blood vessels of the circulation system.

Subunit / interactions. Interacts (via N-terminus) with NOD2. Interacts with CDK2, MCM3, MCM5, MCM7, CDC6 and PCNA. Interacts with MAVS and IFIH1. Interacts (via the second ankyrin repeat cluster) with DDX58. (Microbial infection) Interacts with enterovirus 71/EV71 capsid protein VP1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by CDK2.

Disease relevance. Chopra-Amiel-Gordon syndrome (CAGS) [MIM:619504] An autosomal dominant disorder characterized by developmental delay, intellectual disability, speech delay, and dysmorphic facial features. Additional features include growth failure, feeding difficulties, non-specific brain abnormalities, ophthalmological abnormalities, gait and balance disturbance, joint hypermobility, and predisposition to recurrent infections. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (7)

UniProt ID	Names	Canonical?
O75179-1	1	yes
O75179-2	2
O75179-3	3
O75179-4	4
O75179-5	5
O75179-6	6
O75179-7	7

RefSeq proteins (4): NP_001273700, NP_056389, NP_115593, NP_942592 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR047375	KH-I_ANKRD17	Domain
IPR051631	Ankyrin-KH/SAM_domain	Family

Pfam: PF00013, PF00023, PF12796, PF13637

UniProt features (104 total): repeat 25, compositionally biased region 20, modified residue 20, sequence variant 13, splice variant 9, region of interest 7, sequence conflict 6, chain 1, domain 1, coiled-coil region 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75179-F1	53.73	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 (21): 1, 19, 50, 156, 803, 1457, 1635, 1639, 1696, 1700, 1709, 1874, 2042, 2044, 2045, 2047, 2059, 2067, 2373, 2401 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 386 (showing top): RNGTGGGC_UNKNOWN, GCM_MAP4K4, GCM_PTPRD, GCANCTGNY_MYOD_Q6, SP3_Q3, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MORF_HDAC2, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, chr4q13

GO Biological Process (9): regulation of DNA replication (GO:0006275), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), positive regulation of cell cycle (GO:0045787), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of MDA-5 signaling pathway (GO:1900245), positive regulation of RIG-I signaling pathway (GO:1900246), immune system process (GO:0002376)

GO Molecular Function (4): chromatin binding (GO:0003682), RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), membrane (GO:0016020), nuclear membrane (GO:0031965)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of intracellular signal transduction	3
binding	3
positive regulation of pattern recognition receptor signaling pathway	2
DNA replication	1
regulation of DNA metabolic process	1
defense response	1
response to bacterium	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
immune response	1
defense response to symbiont	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
positive regulation of immune effector process	1
MDA-5 signaling pathway	1
regulation of MDA-5 signaling pathway	1
RIG-I signaling pathway	1
regulation of RIG-I signaling pathway	1
biological_process	1
nucleic acid binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

2092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD17	IGF2BP3	O00425	524
ANKRD17	FOXK2	Q01167	511
ANKRD17	COX18	Q8N8Q8	491
ANKRD17	ASXL2	Q76L83	464
ANKRD17	UBE2O	Q9C0C9	430
ANKRD17	FOXK1	P85037	425
ANKRD17	CCSER2	Q9H7U1	418
ANKRD17	KCNN3	Q9UGI6	396
ANKRD17	ASXL1	Q8IXJ9	395
ANKRD17	CCNA2	P20248	386
ANKRD17	BRD4	O60885	377
ANKRD17	CCNA1	P78396	374
ANKRD17	ANK3	Q12955	370
ANKRD17	HAT1	O14929	369
ANKRD17	ANK2	Q01484	369

IntAct

145 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
ANKRD17	HOXB6	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
RFPL4B	RFPL4A	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
SIX2	EYA2	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
TCEANC2	HTATSF1	psi-mi:“MI:0914”(association)	0.530
HOXD4	ANKRD17	psi-mi:“MI:0914”(association)	0.530
MEAF6	ANKRD17	psi-mi:“MI:0914”(association)	0.530
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
vpr	ANKRD17	psi-mi:“MI:0914”(association)	0.460
ANKRD17	POP1	psi-mi:“MI:0915”(physical association)	0.400
ADH6	ANKRD17	psi-mi:“MI:0915”(physical association)	0.370
ANKRD17	MDM2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (299): ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Co-fractionation), ANKRD17 (Affinity Capture-MS), ANKRD17 (Proximity Label-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ0, A6NGH8, A7E2S9, C7B178, D3J162, D3J163, G5E8K5, L7X8P2, O70511, O75179, O95271, P0DJE3, P16157, P42773, Q01484, Q02357, Q02989, Q08E43, Q12955, Q18297, Q2T9W8, Q3UES3, Q4R3S3, Q4UJJ2, Q54KA7, Q5TYM7, Q5VYY1, Q60772, Q60773, Q641X1, Q65XV2, Q6PFX9, Q71S21, Q7T163, Q8C8R3, Q8UVC1, Q8UVC3, Q92527, Q94B55, Q99NH0

Diamond homologs: A0A0B4KGY6, A6ZKR5, B3LNH0, C5DIR2, C7GND0, C8Z3W4, O00425, O19048, O42254, O57526, O73932, O75179, O88477, P38199, P57721, P57722, P57723, P57724, P60335, Q00341, Q0VCU0, Q15365, Q15366, Q5E9A3, Q5R439, Q5ZLP8, Q61990, Q8CGX0, Q8UVD9, Q96AE4, Q99NH0, Q9CPN8, Q9NZI8, Q9PW80, Q9UNW9, O74919, Q32PX7, Q3U0V1, Q6FUD8, Q8IWZ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 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
Activation of BAD and translocation to mitochondria	7	45.2×	2e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	39.9×	3e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	39.9×	3e-08
Activation of BH3-only proteins	7	29.4×	2e-07
RHO GTPases activate PKNs	9	24.2×	2e-08
Intrinsic Pathway for Apoptosis	7	17.4×	7e-06
SARS-CoV-1-host interactions	10	14.9×	1e-07
FOXO-mediated transcription	5	14.2×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
embryonic skeletal system morphogenesis	7	17.2×	1e-04
protein targeting	6	13.8×	2e-03
anterior/posterior pattern specification	9	10.3×	1e-04
intracellular protein localization	9	5.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	27
Uncertain significance	430
Likely benign	55
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1213834	NM_032217.5(ANKRD17):c.1958-2A>C	Pathogenic
1213836	NM_032217.5(ANKRD17):c.4341_4344del (p.Gln1448fs)	Pathogenic
1325865	NM_032217.5(ANKRD17):c.5360_5363del (p.Gln1787fs)	Pathogenic
1401037	NM_032217.5(ANKRD17):c.4462_4466del (p.Arg1488fs)	Pathogenic
2654823	NM_032217.5(ANKRD17):c.988_989del (p.Gln330fs)	Pathogenic
2691007	NM_032217.5(ANKRD17):c.4442_4448del (p.Arg1481fs)	Pathogenic
2835968	NM_032217.5(ANKRD17):c.1903del (p.Leu634_Met635insTer)	Pathogenic
3254702	NM_032217.5(ANKRD17):c.7504C>T (p.Arg2502Ter)	Pathogenic
3393940	NM_032217.5(ANKRD17):c.6502dup (p.Gln2168fs)	Pathogenic
3394021	NM_032217.5(ANKRD17):c.1483G>T (p.Glu495Ter)	Pathogenic
3765515	NM_032217.5(ANKRD17):c.704+1G>A	Pathogenic
4055239	NM_032217.5(ANKRD17):c.4453_4457del (p.Lys1485fs)	Pathogenic
4082065	NM_032217.5(ANKRD17):c.6774dup (p.Glu2259Ter)	Pathogenic
4101684	NM_032217.5(ANKRD17):c.3070del (p.Asp1024fs)	Pathogenic
4281518	NM_032217.5(ANKRD17):c.4229_4232del (p.Asn1410fs)	Pathogenic
4537142	NM_032217.5(ANKRD17):c.2363T>A (p.Leu788Ter)	Pathogenic
4578445	NM_032217.5(ANKRD17):c.6878del (p.Asn2293fs)	Pathogenic
976319	NM_032217.5(ANKRD17):c.3751_3754del (p.Asn1251fs)	Pathogenic
1213835	NM_032217.5(ANKRD17):c.4091G>C (p.Gly1364Ala)	Likely pathogenic
1333233	NM_032217.5(ANKRD17):c.4828G>T (p.Glu1610Ter)	Likely pathogenic
1342981	NM_032217.5(ANKRD17):c.3359T>G (p.Leu1120Arg)	Likely pathogenic
1342982	NM_032217.5(ANKRD17):c.1556T>C (p.Leu519Pro)	Likely pathogenic
1342983	NM_032217.5(ANKRD17):c.5638T>C (p.Ser1880Pro)	Likely pathogenic
1342985	NM_032217.5(ANKRD17):c.2147T>G (p.Leu716Arg)	Likely pathogenic
1342986	NM_032217.5(ANKRD17):c.3557C>G (p.Pro1186Arg)	Likely pathogenic
1342987	NM_032217.5(ANKRD17):c.7300C>G (p.Arg2434Gly)	Likely pathogenic
1477858	NM_032217.5(ANKRD17):c.2003T>G (p.Leu668Arg)	Likely pathogenic
1498378	NM_032217.5(ANKRD17):c.1952G>A (p.Ser651Asn)	Likely pathogenic
1697300	NM_032217.5(ANKRD17):c.4074G>A (p.Trp1358Ter)	Likely pathogenic
1700059	NM_032217.5(ANKRD17):c.3463T>A (p.Ser1155Thr)	Likely pathogenic

SpliceAI

6403 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73077101:TACC:T	acceptor_gain	1.0000
4:73077103:CC:C	acceptor_gain	1.0000
4:73077104:CCT:C	acceptor_gain	1.0000
4:73077105:C:T	acceptor_gain	1.0000
4:73077106:T:C	acceptor_gain	1.0000
4:73077349:CTTTA:C	donor_loss	1.0000
4:73077350:TTTA:T	donor_loss	1.0000
4:73077351:TTAC:T	donor_loss	1.0000
4:73077352:TA:T	donor_loss	1.0000
4:73077378:AG:A	donor_gain	1.0000
4:73077424:T:TA	donor_gain	1.0000
4:73078890:TC:T	acceptor_loss	1.0000
4:73078891:C:CC	acceptor_gain	1.0000
4:73078892:T:C	acceptor_loss	1.0000
4:73092296:CACCC:C	acceptor_gain	1.0000
4:73092298:CCC:C	acceptor_gain	1.0000
4:73092299:CC:C	acceptor_gain	1.0000
4:73092299:CCC:C	acceptor_gain	1.0000
4:73092300:CC:C	acceptor_gain	1.0000
4:73094082:A:AC	donor_gain	1.0000
4:73094091:AT:A	donor_gain	1.0000
4:73094149:C:CA	donor_gain	1.0000
4:73094225:TGACC:T	acceptor_loss	1.0000
4:73094227:ACCT:A	acceptor_loss	1.0000
4:73094228:CCTG:C	acceptor_loss	1.0000
4:73094229:C:CA	acceptor_loss	1.0000
4:73094230:T:A	acceptor_loss	1.0000
4:73097273:C:CC	acceptor_gain	1.0000
4:73102371:AATAC:A	donor_loss	1.0000
4:73102373:TA:T	donor_loss	1.0000

AlphaMissense

16882 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73092220:A:G	L1803P	1.000
4:73092253:A:G	L1792S	1.000
4:73092257:C:G	A1791P	1.000
4:73092262:A:C	I1789S	1.000
4:73092262:A:T	I1789N	1.000
4:73092274:G:T	A1785E	1.000
4:73092275:C:G	A1785P	1.000
4:73092298:C:A	G1777V	1.000
4:73092298:C:T	G1777D	1.000
4:73092299:C:A	G1777C	1.000
4:73092299:C:G	G1777R	1.000
4:73094082:A:C	I1775R	1.000
4:73094082:A:G	I1775T	1.000
4:73094082:A:T	I1775K	1.000
4:73094088:A:C	I1773S	1.000
4:73094088:A:G	I1773T	1.000
4:73094088:A:T	I1773N	1.000
4:73094094:C:G	R1771P	1.000
4:73094130:A:C	I1759R	1.000
4:73094130:A:T	I1759K	1.000
4:73094136:G:T	A1757E	1.000
4:73094137:C:G	A1757P	1.000
4:73094151:C:G	R1752P	1.000
4:73094154:A:C	I1751S	1.000
4:73094154:A:G	I1751T	1.000
4:73094154:A:T	I1751N	1.000
4:73094158:C:G	A1750P	1.000
4:73094163:A:T	I1748N	1.000
4:73094165:A:C	N1747K	1.000
4:73094165:A:T	N1747K	1.000

dbSNP variants (sampled 300 via entrez): RS1000023133 (4:73177997 C>T), RS1000028889 (4:73220013 T>C), RS1000040193 (4:73110467 T>C), RS1000050398 (4:73252783 T>A,C), RS1000075269 (4:73088146 A>G), RS1000164014 (4:73243299 AGAAT>A), RS1000203565 (4:73159554 T>C), RS1000218674 (4:73112378 G>C), RS1000220626 (4:73217290 AC>A), RS1000246720 (4:73243047 G>C), RS1000268104 (4:73126313 C>T), RS1000291467 (4:73213325 T>A,G), RS1000328481 (4:73157387 C>G,T), RS1000347738 (4:73249427 T>C), RS1000353980 (4:73119612 A>T)

Disease associations

OMIM: gene MIM:615929 | disease phenotypes: MIM:619504, MIM:614116

GenCC curated gene-disease

Disease	Classification	Inheritance
Chopra-Amiel-Gordon syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (4): Chopra-Amiel-Gordon syndrome (MONDO:0859186), hereditary sensory neuropathy-deafness-dementia syndrome (MONDO:0013584), lip and oral cavity carcinoma (MONDO:0023644), intellectual disability (MONDO:0001071)

Orphanet (2): Hereditary sensory neuropathy-deafness-dementia syndrome (Orphanet:456318), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000122	Unilateral renal agenesis
HP:0000175	Cleft palate
HP:0000201	Pierre-Robin sequence
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000454	Flared nostrils
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000582	Upslanted palpebral fissure
HP:0000629	Periorbital fullness
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001382	Joint hypermobility
HP:0002353	EEG abnormality
HP:0002650	Scoliosis
HP:0002719	Recurrent infections
HP:0002750	Delayed skeletal maturation
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0007874	Almond-shaped palpebral fissure
HP:0008897	Postnatal growth retardation

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001942_8	Prostate cancer	5.000000e-13
GCST002361_1	Smooth-surface caries	7.000000e-07
GCST005444_6	Esterified cholesterol levels	6.000000e-09
GCST005481_5	Large LDL particle concentration	5.000000e-09
GCST005483_6	Total cholesterol levels in large LDL	1.000000e-08
GCST005484_4	Cholesterol ester levels in large LDL	1.000000e-08
GCST005485_11	Free cholesterol levels in large LDL	2.000000e-08
GCST005486_6	Medium LDL particle concentration	6.000000e-10
GCST005488_6	Total cholesterol levels in medium LDL	2.000000e-09
GCST005489_7	Cholesterol ester levels in medium LDL	1.000000e-09
GCST005491_19	Total cholesterol levels in small LDL	5.000000e-11
GCST010243_146	Apolipoprotein B levels	8.000000e-09
GCST90002383_389	Hematocrit	1.000000e-09
GCST90002403_424	Red blood cell count	6.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008589	esterified cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008591	free cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C580162	Hereditary Sensory and Autonomic Neuropathy Type Ie (supp.)

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
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
sodium arsenite	affects binding, decreases reaction, increases reaction, decreases activity, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
pentanal	decreases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
abrine	decreases expression	1
brevetoxin 2	decreases expression	1
riccardin D	increases expression	1
Irinotecan	decreases expression	1
Eucalyptol	decreases expression	1
Acetaminophen	decreases expression	1
Arbutin	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Phenolsulfonphthalein	increases expression, affects cotreatment	1
Ribonucleotides	affects binding, decreases reaction	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1JJ	Abcam HeLa ANKRD17 KO	Cancer cell line	Female
CVCL_SC52	HAP1 ANKRD17 (-) 1	Cancer cell line	Male
CVCL_SC53	HAP1 ANKRD17 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01418118	PHASE4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT03017053	PHASE4	UNKNOWN	The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor
NCT03684707	PHASE4	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00158652	PHASE3	COMPLETED	Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC
NCT00158678	PHASE3	COMPLETED	IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC
NCT00402779	PHASE3	COMPLETED	Erlotinib Prevention of Oral Cancer (EPOC)
NCT00655421	PHASE3	UNKNOWN	Oral Cancer Screening in Mumbai, India by Primary Health Care Workers
NCT00750503	PHASE3	COMPLETED	Workplace Tobacco Cessation And Oral Cancer Screening Study
NCT00964977	PHASE3	COMPLETED	Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis.
NCT01039298	PHASE3	UNKNOWN	Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL
NCT03685409	PHASE3	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions
NCT05721755	PHASE3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT06589804	PHASE3	RECRUITING	Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
NCT06737822	PHASE3	RECRUITING	Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:
NCT07402538	PHASE3	NOT_YET_RECRUITING	Surgery With or Without Neoadjuvant Treatment of SBRT Plus Chemoimmunotherapy in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma
NCT07441681	PHASE3	NOT_YET_RECRUITING	Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00330382	PHASE2	COMPLETED	Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
NCT00400205	PHASE2	TERMINATED	Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil
NCT00933387	PHASE2	COMPLETED	A Study of Neoadjuvant Bio-C/T Followed by Concurrent Bio-R/T in High-risk Locally Advanced Oral Squamous Cell Carcinoma
NCT01440270	PHASE2	COMPLETED	Neo-adjuvant Erbitux-based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer
NCT01733797	PHASE2	COMPLETED	Trismus Trial of Therabite vs Wooden Spatula in Head and Neck Cancer Patients
NCT02734537	PHASE2	RECRUITING	Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
NCT02960724	PHASE2	UNKNOWN	uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer
NCT03008694	PHASE2	UNKNOWN	Effect of FDG-PET/CT for Simulation and Radiation Treatment Planning in Oral Cancer Patients
NCT03174275	PHASE2	ACTIVE_NOT_RECRUITING	Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma
NCT03383094	PHASE2	ACTIVE_NOT_RECRUITING	Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
NCT03529422	PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN
NCT04191460	PHASE2	RECRUITING	Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer
NCT04251949	PHASE2	COMPLETED	Evaluation of the Photobiomodulation Using LED Lamp for Curative Treatment of Radio-induced Mucositis.
NCT04541355	PHASE2	COMPLETED	Sodium Thiosulfate in Preventing Ototoxicity for Squamous Cell Cancer Patients Undergoing Chemoradiation With Cisplatin
NCT04862650	PHASE2	ACTIVE_NOT_RECRUITING	Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT05136196	PHASE2	RECRUITING	BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
NCT05172258	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
NCT05456022	PHASE2	UNKNOWN	Therapeutic Efficacy of Quercetin Versus Its Encapsulated Nanoparticle on Tongue Squamous Cell Carcinoma Cell Line
NCT05941338	PHASE2	RECRUITING	Tirelizumab in Combination With Carboplatin and Albumin-binding Paclitaxel for Neoadjuvant Therapy in HNSCC