POGZ

Summary

POGZ (pogo transposable element derived with ZNF domain, HGNC:18801) is a protein-coding gene on chromosome 1q21.3, encoding Pogo transposable element with ZNF domain (Q7Z3K3). Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. It is a selective cancer dependency (DepMap: 26.1% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 23126 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 888 total — 117 pathogenic, 75 likely-pathogenic
• Phenotypes (HPO): 161
• Cancer dependency (DepMap): dependent in 26.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_015100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18801
Approved symbol	POGZ
Name	pogo transposable element derived with ZNF domain
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0461, ZNF635, ZNF280E
Ensembl gene	ENSG00000143442
Ensembl biotype	protein_coding
OMIM	614787
Entrez	23126

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 15 protein_coding, 8 retained_intron, 1 nonsense_mediated_decay

ENST00000271715, ENST00000358476, ENST00000368863, ENST00000392723, ENST00000409503, ENST00000439756, ENST00000441516, ENST00000450842, ENST00000467287, ENST00000476128, ENST00000482678, ENST00000485040, ENST00000491586, ENST00000492528, ENST00000495253, ENST00000497787, ENST00000529669, ENST00000531094, ENST00000533351, ENST00000533461, ENST00000594456, ENST00000703168, ENST00000703169, ENST00000710270

RefSeq mRNA: 6 — MANE Select: NM_015100 NM_001194937, NM_001194938, NM_001410860, NM_015100, NM_145796, NM_207171

CCDS: CCDS44222, CCDS53365, CCDS53366, CCDS91052, CCDS997, CCDS998

Canonical transcript exons

ENST00000271715 — 19 exons

Exon	Start	End
ENSE00001149109	151406607	151406631
ENSE00001149118	151406911	151407023
ENSE00002116752	151442081	151442205
ENSE00003459168	151429603	151429711
ENSE00003488949	151412296	151412396
ENSE00003509277	151407235	151407291
ENSE00003525195	151430666	151430841
ENSE00003558167	151424955	151425061
ENSE00003569754	151402724	151406464
ENSE00003587994	151408409	151408581
ENSE00003597500	151428123	151428413
ENSE00003626420	151408694	151408828
ENSE00003639343	151408100	151408240
ENSE00003654039	151427823	151428041
ENSE00003660918	151423397	151423551
ENSE00003661027	151411625	151411771
ENSE00003668984	151423949	151424286
ENSE00003689512	151440928	151441086
ENSE00004010818	151459152	151459494

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.0739 / max 152.6600, expressed in 1807 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14447	11.6812	1772
14444	4.3967	1549
14442	2.5734	1077
14446	0.8466	523
14445	0.5798	363
14437	0.4385	206
201730	0.2383	87
14443	0.1777	78
14440	0.1416	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.31	gold quality
cerebellar hemisphere	UBERON:0002245	97.21	gold quality
cerebellar cortex	UBERON:0002129	97.18	gold quality
cerebellum	UBERON:0002037	97.10	gold quality
buccal mucosa cell	CL:0002336	97.00	gold quality
sural nerve	UBERON:0015488	96.61	gold quality
left ovary	UBERON:0002119	96.57	gold quality
pituitary gland	UBERON:0000007	96.37	gold quality
ovary	UBERON:0000992	95.98	gold quality
right ovary	UBERON:0002118	95.89	gold quality
adenohypophysis	UBERON:0002196	95.76	gold quality
ganglionic eminence	UBERON:0004023	95.76	gold quality
right lobe of thyroid gland	UBERON:0001119	95.66	gold quality
nerve	UBERON:0001021	95.64	gold quality
tibial nerve	UBERON:0001323	95.64	gold quality
thyroid gland	UBERON:0002046	95.61	gold quality
left lobe of thyroid gland	UBERON:0001120	95.58	gold quality
body of uterus	UBERON:0009853	95.43	gold quality
colonic epithelium	UBERON:0000397	95.40	gold quality
corpus callosum	UBERON:0002336	95.28	gold quality
cortical plate	UBERON:0005343	95.13	gold quality
embryo	UBERON:0000922	95.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.92	gold quality
lower esophagus	UBERON:0013473	94.90	gold quality
tibia	UBERON:0000979	94.89	gold quality
lateral globus pallidus	UBERON:0002476	94.85	gold quality
ventricular zone	UBERON:0003053	94.79	gold quality
endocervix	UBERON:0000458	94.77	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)

174 targeting POGZ, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
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-548N	99.98	71.94	4170

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 26.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• LEDGF/p75 has a role in DDE domain protein function and interacts with the transposase-derived DDE domain of PogZ (PMID:19244240)
• The results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis. (PMID:20562864)
• common LEDGF/p75 interaction interface shared by JPO2, PogZ, MLL1, IWS1 and HIV IN (PMID:26245978)
• Data suggest that loss of function variants in POGZ lead to an identifiable syndrome of neurodevelopmental disorders with specific phenotypic traits including intellectual disability. (PMID:26739615)
• In silico analysis and western blotting revealed this frameshift mutation generating truncated protein in peripheral blood lymphocytes, and this may disrupt several important domains of POGZ gene. Our finding broadens the spectrum of POGZ mutations and may help to understand the molecular basis of Intellectual disability (ID) and aid genetic counseling. (PMID:26763879)
• We find that POGZ is constitutively expressed across most tissues and has significantly higher levels of expression in the cerebellum and the pituitary gland. Disruption of POGZ is associated with intellectual disability and autism spectrum disorders (PMID:26942287)
• the important roles of rare inherited missense variants of POGZ in ASD risk and neuronal development (PMID:31196716)
• De novo likely gene-disrupting variants of POGZ cause autism spectrum disorder (ASD) and intellectual disability. (PMID:31347273)
• Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome). (PMID:31782611)
• A novel patient with White-Sutton syndrome refines the mutational and clinical repertoire of the POGZ-related phenotype and suggests further observations. (PMID:32359026)
• Neuropsychological study in 19 French patients with White-Sutton syndrome and POGZ mutations. (PMID:33277917)
• Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZ(WT/Q1038R) mouse model of autism spectrum disorder. (PMID:33726803)
• Adducted Thumb and Peripheral Polyneuropathy: Diagnostic Supports in Suspecting White-Sutton Syndrome: Case Report and Review of the Literature. (PMID:34206215)
• Identification of abnormally high expression of POGZ as a new biomarker associated with a poor prognosis in osteosarcoma. (PMID:34474553)
• POGZ promotes homology-directed DNA repair in an HP1-dependent manner. (PMID:34758190)
• Autism risk gene POGZ promotes chromatin accessibility and expression of clustered synaptic genes. (PMID:34879283)
• Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring. (PMID:35052493)
• Loss of POGZ alters neural differentiation of human embryonic stem cells. (PMID:35367590)
• Chromodomain on Y-like 2 (CDYL2) implicated in mitosis and genome stability regulation via interaction with CHAMP1 and POGZ. (PMID:36658409)
• Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder. (PMID:38350721)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pogz	ENSMUSG00000038902
rattus_norvegicus	Pogz	ENSRNOG00000053599

Paralogs (12): CENPB (ENSG00000125817), TIGD7 (ENSG00000140993), POGK (ENSG00000143157), TIGD6 (ENSG00000164296), TIGD4 (ENSG00000169989), TIGD3 (ENSG00000173825), TIGD5 (ENSG00000179886), TIGD2 (ENSG00000180346), JRKL (ENSG00000183340), TIGD1 (ENSG00000221944), JRK (ENSG00000234616), (ENSG00000293642)

Protein

Protein identifiers

Pogo transposable element with ZNF domain — Q7Z3K3 (reviewed: Q7Z3K3)

Alternative names: Suppressor of hairy wing homolog 5, Zinc finger protein 280E, Zinc finger protein 635

All UniProt accessions (11): Q7Z3K3, A0A0G2JHK5, A0A8V8TQ67, A0A8V8TQQ8, A0AA34QVU4, A6PW30, E9PIR8, E9PJY9, H0YCT3, H7C238, M0R2X2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms. Promotes the repair of DNA double-strand breaks through the homologous recombination pathway.

Subunit / interactions. Interacts with CBX1, CBX3, MAD2L2 and CHAMP1. Interacts with CBX5; POGZ competes with PXVXL motif-containing proteins such as INCENP and TRIM28 for interaction with CBX5. Interacts (via IBM motif) with PSIP1 isoform 1 (via IBD domain); phosphorylation increases its affinity for PSIP1. Interacts with HDGFL2.

Subcellular location. Nucleus. Chromosome. Cytoplasm.

Post-translational modifications. Phosphorylation increases its interaction with PSIP1.

Disease relevance. Defects in POGZ may be associated with neuropsychiatric disorders such as autism spectrum disorders (ASD), bipolar affective disorders and early dementia onset. ASD are characterized by impairments in reciprocal social interaction and communication as well as restricted and stereotyped patterns of interest and activities. ASD include forms with moderate to severe cognitive impairment and milder forms with higher cognitive ability (Asperger syndrome). White-Sutton syndrome (WHSUS) [MIM:616364] An autosomal dominant syndrome characterized by developmental delay, intellectual disability, hypotonia, behavioral abnormalities, and dysmorphic facial features. Variable features include short stature, microcephaly, strabismus and hearing loss. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (7)

UniProt ID	Names	Canonical?
Q7Z3K3-1	1	yes
Q7Z3K3-2	2
Q7Z3K3-3	3
Q7Z3K3-4	4
Q7Z3K3-5	5, CRA_e
Q7Z3K3-6	6
Q7Z3K3-7	7

RefSeq proteins (6): NP_001181866, NP_001181867, NP_001397789, NP_055915, NP_665739, NP_997054 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004875	DDE_SF_endonuclease_dom	Domain
IPR006600	HTH_CenpB_DNA-bd_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527
IPR057618	Znf_POGZ/Z280C-D-like	Domain
IPR059074	Znf-C2H2_Z280C_D	Domain

Pfam: PF03184, PF03221, PF25414, PF25429

UniProt features (86 total): modified residue 17, sequence conflict 12, zinc finger region 9, cross-link 9, region of interest 8, mutagenesis site 8, compositionally biased region 6, splice variant 6, domain 2, sequence variant 2, turn 2, helix 2, chain 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2E72	SOLUTION NMR
2N3A	SOLUTION NMR
6EMP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3K3-F1	58.48	0.09

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 (26): 333, 363, 425, 439, 445, 463, 856, 1338, 1364, 1367, 1368, 1373, 1374, 1378, 1392, 1394, 1396, 319, 359, 422 …

Mutagenesis-validated functional residues (8):

Position	Phenotype
817	diminishes interaction with cbx5 and abolishes interaction with cbx1 and cbx5; when associated with a-820; a-833 and a-8
820	abolishes interaction with cbx1, cbx3 and cbx5; when associated with when associated with a-817; a-833 and a-840.
833	abolishes interaction with cbx1, cbx3 and cbx5; when associated with a-817; a-820 and a-840.
840	abolishes interaction with cbx1, cbx3 and cbx5; when associated with a-817; a-820 and a-833.
1392	loss of phosphorylation. loss of interaction with psip1; when associated with a-1396.
1392	phosphomimetic mutant. significant increase in interaction with psip1; when associated with d-1396.
1396	loss of phosphorylation. loss of interaction with psip1; when associated with a-1392.
1396	phosphomimetic mutant. significant increase in interaction with psip1; when associated with d-1392.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 549 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GCM_MAP4K4, WANG_CLIM2_TARGETS_UP, HNF3ALPHA_Q6, GCM_GSPT1, CMYB_01, MAZ_Q6, CHX10_01, GGGTGGRR_PAX4_03, FOXD3_01, FREAC3_01, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_SISTER_CHROMATID_COHESION, HFH8_01, FOXJ2_01

GO Biological Process (8): double-strand break repair via homologous recombination (GO:0000724), mitotic sister chromatid cohesion (GO:0007064), positive regulation of transcription by RNA polymerase II (GO:0045944), cell division (GO:0051301), kinetochore assembly (GO:0051382), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974)

GO Molecular Function (5): DNA binding (GO:0003677), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), ciliary basal body (GO:0036064), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	2
binding	2
recombinational repair	1
double-strand break repair	1
sister chromatid cohesion	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular process	1
kinetochore organization	1
protein-containing complex assembly	1
membraneless organelle assembly	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
microtubule organizing center	1
cilium	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POGZ	PSIP1	O75475	642
POGZ	ZNF81	P51508	596
POGZ	CHAMP1	Q96JM3	576
POGZ	PPIE	Q9UNP9	488
POGZ	CDCA7L	Q96GN5	479
POGZ	MEN1	O00255	476
POGZ	CHD8	Q9HCK8	460
POGZ	ZNF292	O60281	447
POGZ	CBX1	P23197	432
POGZ	ZBTB20	Q9HC78	416
POGZ	ZNF674	Q2M3X9	414
POGZ	CBX5	P45973	413
POGZ	CBX3	Q13185	411
POGZ	KLF7	O75840	410
POGZ	CHD4	Q14839	410

IntAct

489 interactions, top by confidence:

A	B	Type	Score
BANP	POGZ	psi-mi:“MI:0915”(physical association)	0.780
POGZ	BANP	psi-mi:“MI:0915”(physical association)	0.780
ZBTB24	POGZ	psi-mi:“MI:0915”(physical association)	0.720
POGZ	HGS	psi-mi:“MI:0915”(physical association)	0.720
POGZ	DAZAP2	psi-mi:“MI:0915”(physical association)	0.720
POGZ	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
HGS	POGZ	psi-mi:“MI:0915”(physical association)	0.720
NRF1	POGZ	psi-mi:“MI:0915”(physical association)	0.700
QRICH1	POGZ	psi-mi:“MI:0915”(physical association)	0.700
POGZ	RBPMS	psi-mi:“MI:0915”(physical association)	0.700
POGZ	NRF1	psi-mi:“MI:0915”(physical association)	0.700
POGZ	QRICH1	psi-mi:“MI:0915”(physical association)	0.700
RBPMS	POGZ	psi-mi:“MI:0915”(physical association)	0.700
POGZ	ZXDC	psi-mi:“MI:0915”(physical association)	0.670
POGZ	GABPB1	psi-mi:“MI:0915”(physical association)	0.560
POGZ	NRF1	psi-mi:“MI:0915”(physical association)	0.560
POGZ	DAB1	psi-mi:“MI:0915”(physical association)	0.560
POU2F1	POGZ	psi-mi:“MI:0915”(physical association)	0.560
POGZ	NFYA	psi-mi:“MI:0915”(physical association)	0.560
PRR20C	POGZ	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	POGZ	psi-mi:“MI:0915”(physical association)	0.560
BANP	POGZ	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	POGZ	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (359): POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), POGZ (Two-hybrid), BANP (Two-hybrid), ZXDC (Two-hybrid), PRR20A (Two-hybrid), POGZ (Affinity Capture-RNA), POGZ (Affinity Capture-RNA), POGZ (Affinity Capture-RNA)

ESM2 similar proteins: A0A1L8GR68, A2A791, B2GUN4, E1BP74, E1BZ85, F1QLG5, F7AQ22, O00472, O15164, O15550, O70546, O88974, O95789, P49140, P55265, P70365, Q14202, Q14596, Q15047, Q15788, Q4PJW2, Q5R413, Q5RC94, Q5RDJ2, Q5VZL5, Q64127, Q69Z66, Q6H8Q1, Q6KC51, Q6NXK2, Q6P3Y5, Q6PFK1, Q7Z3K3, Q8BJ34, Q8BL65, Q8BZH4, Q8CHY6, Q8IZD4, Q8TEW8, Q8VIG2

Diamond homologs: P59817, Q5PPG4, Q68FE8, Q6N043, Q6P3Y5, Q7Z3K3, Q86YH2, Q8BZH4, Q8ND82, Q99KZ6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
POGZ	“down-regulates activity”	CBX5	binding
POGZ	“up-regulates activity”	AURKB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
PPARA activates gene expression	6	12.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	117
Likely pathogenic	75
Uncertain significance	367
Likely benign	145
Benign	59

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032656	NM_015100.4(POGZ):c.2768dup (p.His923fs)	Pathogenic
1071988	NM_015100.4(POGZ):c.733C>T (p.Gln245Ter)	Pathogenic
1164015	NM_015100.4(POGZ):c.3040C>T (p.Gln1014Ter)	Pathogenic
1172624	NM_015100.4(POGZ):c.3121C>T (p.Gln1041Ter)	Pathogenic
1184125	NM_015100.4(POGZ):c.566del (p.Pro189fs)	Pathogenic
1184127	NM_015100.4(POGZ):c.3312del (p.Phe1104fs)	Pathogenic
1184815	NM_015100.4(POGZ):c.1679-3C>G	Pathogenic
1201699	NM_015100.4(POGZ):c.1838A>G (p.His613Arg)	Pathogenic
1299665	NM_015100.4(POGZ):c.3351dup (p.Pro1118fs)	Pathogenic
1323483	NM_015100.4(POGZ):c.2570+1G>T	Pathogenic
1334988	NM_015100.4(POGZ):c.2742_2743dup (p.Ala915fs)	Pathogenic
1343160	NM_015100.4(POGZ):c.460-2A>C	Pathogenic
1684515	NM_015100.4(POGZ):c.2700_2710del (p.Leu901fs)	Pathogenic
1700311	NM_015100.4(POGZ):c.2635_2638del (p.Phe879fs)	Pathogenic
1701130	GRCh37/hg19 1q21.3(chr1:151372064-151384872)x1	Pathogenic
1705564	NM_015100.4(POGZ):c.2709del (p.Pro903_Leu904insTer)	Pathogenic
1710349	NM_015100.4(POGZ):c.1053del (p.Ser352fs)	Pathogenic
1710479	NM_015100.4(POGZ):c.2022dup (p.Lys675Ter)	Pathogenic
1730549	NM_015100.4(POGZ):c.3356T>A (p.Leu1119Ter)	Pathogenic
1789395	NM_015100.4(POGZ):c.2309dup (p.Tyr770Ter)	Pathogenic
1803698	NM_015100.4(POGZ):c.1679-1G>A	Pathogenic
1804028	NM_015100.4(POGZ):c.2819_2826del (p.Leu940fs)	Pathogenic
1878837	NM_015100.4(POGZ):c.410_411del (p.His137fs)	Pathogenic
1878940	NM_015100.4(POGZ):c.1779G>C (p.Gln593His)	Pathogenic
190307	NM_015100.4(POGZ):c.3354del (p.Leu1119fs)	Pathogenic
190308	NM_015100.4(POGZ):c.2711T>A (p.Leu904Ter)	Pathogenic
207797	NM_015100.4(POGZ):c.2750dup (p.Pro918fs)	Pathogenic
207800	NM_015100.4(POGZ):c.2195_2196del (p.Pro732fs)	Pathogenic
218146	NM_015100.4(POGZ):c.2321_2324del (p.Ser774fs)	Pathogenic
218147	NM_015100.4(POGZ):c.2763dup (p.Thr922fs)	Pathogenic

SpliceAI

2326 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151406462:TGC:T	acceptor_gain	1.0000
1:151406463:GCCTA:G	acceptor_loss	1.0000
1:151406464:CCTA:C	acceptor_loss	1.0000
1:151406465:C:CC	acceptor_gain	1.0000
1:151406465:CTAA:C	acceptor_loss	1.0000
1:151406466:T:A	acceptor_loss	1.0000
1:151406907:TTAC:T	donor_loss	1.0000
1:151406908:TAC:T	donor_loss	1.0000
1:151406909:A:AC	donor_gain	1.0000
1:151406909:AC:A	donor_gain	1.0000
1:151406909:ACC:A	donor_gain	1.0000
1:151406909:ACCC:A	donor_gain	1.0000
1:151406910:C:CC	donor_gain	1.0000
1:151406910:CC:C	donor_gain	1.0000
1:151406910:CCC:C	donor_gain	1.0000
1:151406910:CCCC:C	donor_gain	1.0000
1:151407019:TTCCA:T	acceptor_gain	1.0000
1:151407020:TCCA:T	acceptor_gain	1.0000
1:151407021:CCA:C	acceptor_gain	1.0000
1:151407021:CCAC:C	acceptor_gain	1.0000
1:151407022:CA:C	acceptor_gain	1.0000
1:151407022:CAC:C	acceptor_gain	1.0000
1:151407023:ACTAA:A	acceptor_loss	1.0000
1:151407024:C:CC	acceptor_gain	1.0000
1:151407024:CT:C	acceptor_loss	1.0000
1:151407025:T:C	acceptor_loss	1.0000
1:151407289:TTG:T	acceptor_gain	1.0000
1:151407290:TG:T	acceptor_gain	1.0000
1:151407292:C:CC	acceptor_gain	1.0000
1:151408096:TTAC:T	donor_loss	1.0000

AlphaMissense

9223 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151405811:A:G	F1075S	1.000
1:151405820:G:T	A1072D	1.000
1:151405822:C:A	W1071C	1.000
1:151405822:C:G	W1071C	1.000
1:151405824:A:G	W1071R	1.000
1:151405824:A:T	W1071R	1.000
1:151405874:G:T	A1054D	1.000
1:151405883:A:G	F1051S	1.000
1:151405933:C:A	W1034C	1.000
1:151405933:C:G	W1034C	1.000
1:151405935:A:G	W1034R	1.000
1:151405935:A:T	W1034R	1.000
1:151405943:A:G	L1031P	1.000
1:151406019:A:G	W1006R	1.000
1:151406019:A:T	W1006R	1.000
1:151406090:A:G	L982P	1.000
1:151406102:A:G	L978P	1.000
1:151406996:A:C	C820W	1.000
1:151407005:G:C	C817W	1.000
1:151407006:C:T	C817Y	1.000
1:151407007:A:G	C817R	1.000
1:151407283:A:T	V795D	1.000
1:151407285:A:C	H794Q	1.000
1:151407285:A:T	H794Q	1.000
1:151407286:T:A	H794L	1.000
1:151407286:T:C	H794R	1.000
1:151407287:G:A	H794Y	1.000
1:151407287:G:C	H794D	1.000
1:151407287:G:T	H794N	1.000
1:151408103:A:C	I791S	1.000

dbSNP variants (sampled 300 via entrez): RS1000059462 (1:151447780 G>GT), RS1000073609 (1:151444204 G>A,C,T), RS1000075096 (1:151432351 T>C), RS1000122672 (1:151430608 T>C), RS1000157122 (1:151430401 A>T), RS1000166345 (1:151408661 T>A,C), RS1000329617 (1:151424413 GTT>G,GT,GTTT), RS1000468386 (1:151418019 C>G), RS1000521612 (1:151447415 A>C), RS1000551793 (1:151426997 C>T), RS1000577882 (1:151443364 C>T), RS1000596730 (1:151455755 T>C,G), RS1000651624 (1:151443105 G>A,C,T), RS1000661253 (1:151420242 A>G), RS1000675863 (1:151433501 G>A,C,T)

Disease associations

OMIM: gene MIM:614787 | disease phenotypes: MIM:616364, MIM:160700

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Definitive	AD

Mondo (11): intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (MONDO:0014606), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), myopia (MONDO:0001384), hearing loss disorder (MONDO:0005365), hypothyroidism (MONDO:0005420), microcephaly (MONDO:0001149), strabismus (MONDO:0003432), sensorineural hearing loss disorder (MONDO:0020678), obesity disorder (MONDO:0011122)

Orphanet (6): White-Sutton syndrome (Orphanet:468678), Non-syndromic bicoronal craniosynostosis (Orphanet:35099), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

161 total (30 of 161 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000081	Duplicated collecting system
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000356	Abnormality of the outer ear
HP:0000358	Posteriorly rotated ears

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002041_2	Blood trace element (Cu levels)	3.000000e-20
GCST005951_38	Body mass index	4.000000e-09
GCST007269_25	Pulse pressure	4.000000e-08
GCST010397_41	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005267	serum copper measurement
EFO:0004340	body mass index
EFO:0005763	pulse pressure measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D007037	Hypothyroidism	C19.874.482
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009216	Myopia	C11.744.636
D065886	Neurodevelopmental Disorders	F03.625
D013285	Strabismus	C10.292.562.887; C11.590.810

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
sodium arsenite	affects cotreatment, decreases expression, increases abundance	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Ozone	increases abundance, affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Irinotecan	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE85	HAP1 POGZ (-) 1	Cancer cell line	Male
CVCL_TE86	HAP1 POGZ (-) 2	Cancer cell line	Male
CVCL_TE87	HAP1 POGZ (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study