POGZ
gene geneOn this page
Also known as KIAA0461ZNF635ZNF280E
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): 959 total — 115 pathogenic, 89 likely-pathogenic (top 3% of genes corpus-wide)
- Regional missense constraint (gnomAD): 4 of 10 regions constrained (≈12% of expected missense variation)
- GTEx eGene: eQTL in 44 tissues, sQTL in 2 (q < 0.05)
- Phenotypes (HPO): 161
- Cancer dependency (DepMap): dependent in 26.1% of screened cell lines
- Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
- Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.20 (highly constrained)
- 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
MANE Select: ENST00000271715
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 6, TSL 3: 4, TSL 4: 2, TSL 5: 4
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.
Highest expression (Bgee): uterine tube, hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum.
Genetic regulation across tissues (GTEx eQTL / sQTL)
POGZ is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 46 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Nerve Tibial | eqtl | 4.1e-44 | +0.23 | 1:151458279:T:C |
| Whole Blood | eqtl | 6.5e-34 | -0.26 | 1:151452495:T:C |
| Artery Tibial | eqtl | 1.9e-26 | +0.21 | 1:151458279:T:C |
| Muscle Skeletal | eqtl | 9.4e-26 | -0.31 | 1:151470383:C:T |
| Cells Cultured fibroblasts | eqtl | 2.3e-25 | -0.21 | 1:151423306:T:C |
| Testis | eqtl | 2.5e-22 | +0.26 | 1:151420952:C:G |
| Adipose Subcutaneous | eqtl | 7.2e-20 | +0.18 | 1:151458279:T:C |
| Esophagus Gastroesophageal Junction | eqtl | 9.3e-20 | +0.25 | 1:151458279:T:C |
| Artery Aorta | eqtl | 1.9e-18 | +0.20 | 1:151458279:T:C |
| Breast Mammary Tissue | eqtl | 6.6e-17 | +0.22 | 1:151458279:T:C |
| Thyroid | eqtl | 1.5e-16 | +0.16 | 1:151410845:C:T |
| Skin Not Sun Exposed Suprapubic | eqtl | 2.1e-16 | +0.23 | 1:151463465:C:T |
| Brain Cerebellum | eqtl | 2.0e-15 | -0.47 | 1:151412235:A:G |
| Adipose Visceral Omentum | eqtl | 1.0e-14 | +0.16 | 1:151420952:C:G |
| Skin Sun Exposed Lower leg | eqtl | 5.7e-14 | -0.21 | 1:151402069:C:T |
| Esophagus Mucosa | eqtl | 1.3e-13 | +0.16 | 1:151410845:C:T |
| Brain Cerebellar Hemisphere | eqtl | 4.3e-13 | -0.34 | 1:151458228:A:G |
| Colon Sigmoid | eqtl | 1.0e-12 | +0.19 | 1:151458279:T:C |
| Esophagus Muscularis | eqtl | 1.7e-11 | -0.15 | 1:151423306:T:C |
| Heart Atrial Appendage | eqtl | 3.1e-09 | +0.20 | 1:151458279:T:C |
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
showing 100 of 302 tissues 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 |
| caput epididymis | UBERON:0004358 | 94.74 | gold quality |
| paraflocculus | UBERON:0005351 | 94.69 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 94.65 | gold quality |
| metanephros cortex | UBERON:0010533 | 94.64 | gold quality |
| corpus epididymis | UBERON:0004359 | 94.34 | gold quality |
| hair follicle | UBERON:0002073 | 94.17 | gold quality |
| mucosa of stomach | UBERON:0001199 | 94.11 | gold quality |
| adrenal tissue | UBERON:0018303 | 94.11 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 94.06 | gold quality |
| right frontal lobe | UBERON:0002810 | 93.98 | gold quality |
| fundus of stomach | UBERON:0001160 | 93.95 | gold quality |
| inferior olivary complex | UBERON:0002127 | 93.82 | gold quality |
| right coronary artery | UBERON:0001625 | 93.80 | gold quality |
| cauda epididymis | UBERON:0004360 | 93.80 | gold quality |
| inferior vagus X ganglion | UBERON:0005363 | 93.79 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 93.73 | gold quality |
| left uterine tube | UBERON:0001303 | 93.72 | gold quality |
| right adrenal gland | UBERON:0001233 | 93.71 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 93.67 | gold quality |
| renal medulla | UBERON:0000362 | 93.65 | gold quality |
| superficial temporal artery | UBERON:0001614 | 93.55 | gold quality |
| endometrium epithelium | UBERON:0004811 | 93.50 | gold quality |
| CA1 field of hippocampus | UBERON:0003881 | 93.49 | gold quality |
| bone marrow cell | CL:0002092 | 93.48 | gold quality |
| prostate gland | UBERON:0002367 | 93.45 | gold quality |
| spinal cord | UBERON:0002240 | 93.43 | gold quality |
| vagina | UBERON:0000996 | 93.41 | gold quality |
| middle frontal gyrus | UBERON:0002702 | 93.41 | gold quality |
| subthalamic nucleus | UBERON:0001906 | 93.37 | gold quality |
| body of pancreas | UBERON:0001150 | 93.29 | gold quality |
| cerebellar vermis | UBERON:0004720 | 93.26 | gold quality |
| sigmoid colon | UBERON:0001159 | 93.21 | gold quality |
| adrenal cortex | UBERON:0001235 | 93.21 | gold quality |
| right testis | UBERON:0004534 | 93.19 | gold quality |
| female reproductive system | UBERON:0000474 | 93.17 | gold quality |
| myometrium | UBERON:0001296 | 93.16 | gold quality |
| trigeminal ganglion | UBERON:0001675 | 93.13 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 93.13 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 93.13 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 93.10 | gold quality |
| primary visual cortex | UBERON:0002436 | 93.06 | gold quality |
| ectocervix | UBERON:0012249 | 93.05 | gold quality |
| stomach | UBERON:0000945 | 93.04 | gold quality |
| stromal cell of endometrium | CL:0002255 | 92.95 | gold quality |
| left adrenal gland | UBERON:0001234 | 92.91 | gold quality |
| medulla oblongata | UBERON:0001896 | 92.90 | gold quality |
| left testis | UBERON:0004533 | 92.90 | gold quality |
| uterus | UBERON:0000995 | 92.82 | gold quality |
| occipital lobe | UBERON:0002021 | 92.81 | gold quality |
| adrenal gland | UBERON:0002369 | 92.80 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 92.76 | gold quality |
| central nervous system | UBERON:0001017 | 92.72 | gold quality |
| body of stomach | UBERON:0001161 | 92.72 | gold quality |
| testis | UBERON:0000473 | 92.71 | gold quality |
| brain | UBERON:0000955 | 92.70 | gold quality |
| minor salivary gland | UBERON:0001830 | 92.59 | gold quality |
| caudate nucleus | UBERON:0001873 | 92.57 | gold quality |
| postcentral gyrus | UBERON:0002581 | 92.49 | gold quality |
| esophagus | UBERON:0001043 | 92.48 | gold quality |
| popliteal artery | UBERON:0002250 | 92.47 | gold quality |
| tibial artery | UBERON:0007610 | 92.47 | gold quality |
| cardia of stomach | UBERON:0001162 | 92.46 | gold quality |
| nucleus accumbens | UBERON:0001882 | 92.46 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 92.43 | gold quality |
| parietal lobe | UBERON:0001872 | 92.41 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 92.33 | gold quality |
| dorsal plus ventral thalamus | UBERON:0001897 | 92.30 | gold quality |
| peritoneum | UBERON:0002358 | 92.26 | gold quality |
| omental fat pad | UBERON:0010414 | 92.26 | gold quality |
| coronary artery | UBERON:0001621 | 92.23 | 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 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 80 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Postcentral gyrus | tissue | 80.4 | |
| Nucleus accumbens | tissue | 80.1 | |
| Locus coeruleus | tissue | 73.0 | |
| Hippocampus | tissue | 72.5 | high |
| Choroid plexus | tissue | 64.0 | |
| Pituitary gland | tissue | 58.4 | |
| Epididymis | tissue | 46.5 | high |
| Retina | tissue | 41.5 | |
| Ovary | tissue | 35.1 | medium |
| Bone marrow | tissue | 34.5 | high |
| Endometrium 1 | tissue | 31.2 | high |
| Vagina | tissue | 31.0 | high |
| Fallopian tube | tissue | 29.6 | medium |
| Parathyroid gland | tissue | 28.6 | medium |
| Skin 1 | tissue | 28.0 | high |
| Cerebellum | tissue | 26.1 | high |
| Smooth muscle | tissue | 25.5 | medium |
| Breast | tissue | 23.8 | high |
| Thymus | tissue | 23.7 | |
| Testis | tissue | 23.1 | high |
| Thyroid gland | tissue | 22.7 | high |
| Skeletal muscle | tissue | 22.6 | medium |
| Seminal vesicle | tissue | 21.5 | medium |
| Spleen | tissue | 21.2 | medium |
| Olfactory bulb | tissue | 21.1 | |
| Caudate putamen | tissue | 20.2 | |
| Cervix | tissue | 19.9 | high |
| Prostate | tissue | 19.8 | low |
| Tonsil | tissue | 19.7 | medium |
| Salivary gland | tissue | 19.6 | high |
| Gallbladder | tissue | 19.6 | high |
| Tongue | tissue | 19.0 | |
| Adrenal gland | tissue | 18.9 | high |
| Lymph node | tissue | 18.7 | medium |
| Lung | tissue | 18.5 | high |
| Basal ganglia | tissue | 18.3 | high |
| Pancreas | tissue | 18.2 | low |
| Spinal cord | tissue | 18.2 | |
| Hippocampal formation | tissue | 18.2 | |
| Rectum | tissue | 18.0 | high |
| Hypothalamus | tissue | 17.9 | |
| Ventral forebrain | tissue | 17.9 | |
| Septum | tissue | 17.8 | |
| Midbrain | tissue | 17.1 | |
| Thalamus | tissue | 17.1 | |
| Corpus callosum | tissue | 17.0 | |
| Prefrontal cortex | tissue | 16.9 | |
| Cerebral cortex | tissue | 16.9 | high |
| Somatosensory cortex | tissue | 16.9 | |
| Putamen | tissue | 16.6 | |
| Superior colliculi | tissue | 16.6 | |
| Periaqueductal gray | tissue | 16.5 | |
| Substantia nigra | tissue | 16.4 | |
| Motor cortex | tissue | 16.3 | |
| Amygdala | tissue | 16.3 | |
| Entorhinal cortex | tissue | 16.3 | |
| Occipital cortex | tissue | 16.2 | |
| Insular cortex | tissue | 16.2 | |
| Adipose tissue | tissue | 16.1 | medium |
| Medulla oblongata | tissue | 16.1 |
Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (137.2), Temporal white matter (127.7), Flocculonodular lobe (117.5), Cerebellar cortex (113.2), Corpus callosum, splenium (white matter) (113.2).
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
Targeting POGZ by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 174 miRNAs:
| 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
gnomAD constraint: pLI 1, LOEUF 0.198, missense Z 4.15 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD)
ENST00000271715 splits into 10 regions with different missense tolerance; 4 are missense-constrained (≈12% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD
| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
|---|---|---|---|
| 1:151,404,805–151,405,056 | 107 / 97.9 | 1.09 | no |
| 1:151,405,057–151,405,322 | 67 / 105.8 | 0.63 | no |
| 1:151,405,323–151,405,361 | 3 / 18.1 | 0.17 | yes (p 3.8e-04) |
| 1:151,405,362–151,405,804 | 161 / 185.4 | 0.87 | no |
| 1:151,405,805–151,405,972 | 24 / 69.6 | 0.34 | yes (p 4.6e-08) |
| 1:151,405,973–151,406,989 | 214 / 255.5 | 0.84 | no |
| 1:151,406,990–151,408,231 | 34 / 95.5 | 0.36 | yes (p 3.1e-10) |
| 1:151,408,232–151,412,392 | 149 / 237.5 | 0.63 | no |
| 1:151,412,393–151,442,147 | 541 / 680.5 | 0.80 | no |
| 1:151,442,148–151,442,204 | 6 / 23.9 | 0.25 | yes (p 2.5e-04) |
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. |
Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NZM42 (-1.343), LNZTA3WT4 (-1.1), UM-UC9 (-1.096), CCK-81 (-1.083), NCI-H1573 (-1.016), Caov-4 (-0.998), KYAE-1 (-0.974), RERF-GC-1B (-0.971), Caki-1 (-0.969), HEC-116 (-0.964), Hs 695T (-0.96), SK-N-FI (-0.953), JURKAT (-0.951), JEG-3 (-0.951), MHH-NB-11 (-0.92).
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)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:2442117) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 26 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| liver hypoplasia | 1 |
| decreased brain size | 1 |
| abnormal somatosensory cortex morphology | 1 |
| decreased body weight | 1 |
| decreased body size | 1 |
| increased grooming behavior | 1 |
| abnormal vocalization | 1 |
| anemia | 1 |
| abnormal associative learning | 1 |
| decreased brain weight | 1 |
| abnormal response to novel object | 1 |
| decreased fetal size | 1 |
| abnormal behavior | 1 |
| impaired contextual conditioning behavior | 1 |
| decreased birth body size | 1 |
| ventricular septal defect | 1 |
| prenatal lethality, complete penetrance | 1 |
| preweaning lethality, complete penetrance | 1 |
| embryonic lethality during organogenesis, incomplete penetrance | 1 |
| lethality throughout fetal growth and development, incomplete penetrance | 1 |
| abnormal behavioral response to light | 1 |
| decreased forebrain size | 1 |
| increased excitatory postsynaptic current frequency | 1 |
| abnormal response to social novelty | 1 |
| increased dendritic spine density | 1 |
+1 more (showing top 25).
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| PSMB4 | protein-coding | 5692 |
| CGN | protein-coding | 57530 |
| MIR554 | ncRNA | 693139 |
| TUFT1 | protein-coding | 7286 |
| SELENBP1 | protein-coding | 8991 |
| RFX5-AS1 | ncRNA | 101927886 |
| PI4KB | protein-coding | 5298 |
| RFX5 | protein-coding | 5993 |
| SNX27 | protein-coding | 81609 |
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): A0A0G2JHK5, A0A8V8TQ67, A0A8V8TQQ8, A0AA34QVU4, A6PW30, E9PIR8, E9PJY9, Q7Z3K3, 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 | Zf-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 (87 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, helix 3, domain 2, sequence variant 2, turn 2, chain 1, coiled-coil region 1, short sequence motif 1
Structure
Experimental structures (PDB)
3 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 2E72 | Solution structure of the zinc finger domain of human KIAA0461 | SOLUTION NMR | |
| 2N3A | Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404) | SOLUTION NMR | |
| 6EMP | Solution structure of the LEDGF/p75 IBD - POGZ (aa 1370-1404) complex | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q7Z3K3-F1 | 58.48 | 0.09 |
Human Protein Atlas
Protein class: Predicted intracellular proteins, Plasma proteins, Transcription factors, Zinc-coordinating DNA-binding domains, Disease related genes
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): nucleoplasm; basal body; cytosol; plasma membrane
Antibody reliability (HPA): IH enhanced · IF supported
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)
| Type | Positions |
|---|---|
| Phosphoserine | 333, 363, 425, 445, 856, 1338, 1364, 1367, 1373, 1374, 1392, 1396 |
| Phosphothreonine | 439, 463, 1368, 1378, 1394 |
| Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2) | 319, 359, 422, 449, 489, 629, 677, 801, 883 |
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-840. |
| 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 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
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), regulation of DNA-templated transcription (GO:0006355), mitotic sister chromatid cohesion (GO:0007064), cell division (GO:0051301), kinetochore assembly (GO:0051382), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974)
GO Molecular Function (7): transcription cis-regulatory region binding (GO:0000976), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)
GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), chromosome (GO:0005694)
GO top-level categories
29 GO namespaces:
| Category | Terms |
|---|---|
| cellular anatomical structure | 4 |
| DNA metabolic process | 2 |
| binding | 2 |
| recombinational repair | 1 |
| double-strand break repair | 1 |
| DNA-templated transcription | 1 |
| regulation of gene expression | 1 |
| regulation of RNA biosynthetic process | 1 |
| sister chromatid cohesion | 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 |
| transcription regulatory region nucleic acid binding | 1 |
| sequence-specific double-stranded DNA binding | 1 |
| transcription cis-regulatory region binding | 1 |
| regulation of DNA-templated transcription | 1 |
| transcription regulator activity | 1 |
| transition metal ion binding | 1 |
| nucleic acid binding | 1 |
| cation binding | 1 |
| chromosome | 1 |
| intracellular membrane-bounded organelle | 1 |
| nuclear lumen | 1 |
| intracellular anatomical structure | 1 |
| cytoplasm | 1 |
| intracellular membraneless organelle | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).
8 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| double-strand break repair via homologous recombination | BP | mutant phenotype |
| kinetochore assembly | BP | mutant phenotype |
| mitotic sister chromatid cohesion | BP | mutant phenotype |
| chromatin | CC | direct assay |
| cytoplasm | CC | direct assay |
| cytosol | CC | direct assay |
| nucleoplasm | CC | direct assay |
| nucleus | CC | direct assay |
Protein interactions and networks
STRING
showing 15 of 1,188 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| POGZ | PSIP1 | O75475 | 537 |
| POGZ | TIGD2 | Q4W5G0 | 529 |
| POGZ | JRKL | Q9Y4A0 | 521 |
| POGZ | ZNF81 | P51508 | 479 |
| POGZ | MEN1 | O00255 | 472 |
| POGZ | CHAMP1 | Q96JM3 | 468 |
| POGZ | RASIP1 | Q5U651 | 452 |
| POGZ | CBX5 | P45973 | 449 |
| POGZ | CBX1 | P23197 | 433 |
| POGZ | CDCA7L | Q96GN5 | 425 |
| POGZ | UPF3B | Q9BZI7 | 423 |
| POGZ | CENPBD1P | B2RD01 | 422 |
| POGZ | CBX3 | Q13185 | 407 |
| POGZ | CHD4 | Q14839 | 407 |
| POGZ | SP1 | P08047 | 404 |
IntAct
Human interaction partners of POGZ in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
showing 30 of 86 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| BANP | physical association | 0.780 | 21 |
| CBX5 | association | 0.780 | 3 |
| DAZAP2 | physical association | 0.720 | 8 |
| ZBTB24 | physical association | 0.720 | 8 |
| HGS | physical association | 0.720 | 6 |
| NRF1 | physical association | 0.700 | 10 |
| RBPMS | physical association | 0.700 | 8 |
| QRICH1 | physical association | 0.700 | 7 |
| ZXDC | physical association | 0.670 | 4 |
| FNDC3B | physical association | 0.560 | 6 |
| NFYA | physical association | 0.560 | 6 |
| C10orf55 | physical association | 0.560 | 5 |
| GABPB1 | physical association | 0.560 | 5 |
| KRTAP6-2 | physical association | 0.560 | 5 |
| KRTAP8-1 | physical association | 0.560 | 5 |
| RBFOX1 | physical association | 0.560 | 5 |
| NFYC | physical association | 0.560 | 4 |
| A1CF | physical association | 0.560 | 3 |
| ACTMAP | physical association | 0.560 | 3 |
| AGR2 | physical association | 0.560 | 3 |
| ANKRD10 | physical association | 0.560 | 3 |
| AOC1 | physical association | 0.560 | 3 |
| ASB13 | physical association | 0.560 | 3 |
| ATXN1 | physical association | 0.560 | 3 |
| BOLL | physical association | 0.560 | 3 |
| CERCAM | physical association | 0.560 | 3 |
| CRX | physical association | 0.560 | 3 |
| DAB1 | physical association | 0.560 | 3 |
| DMXL1 | physical association | 0.560 | 3 |
| DTX2 | physical association | 0.560 | 3 |
BioGRID (369 interactions; top human partners by supporting records): CBX3 (Affinity Capture-MS; 10 records), CBX5 (Affinity Capture-MS; 8 records), MAD2L2 (Affinity Capture-MS; 8 records), CBX1 (Affinity Capture-MS; 7 records), CHAMP1 (Affinity Capture-MS; 5 records), CREB1 (Two-hybrid; 4 records), HDGFRP2 (Affinity Capture-MS; 4 records), BANP (Two-hybrid; 3 records), NFYC (Two-hybrid; 3 records), NRF1 (Two-hybrid; 3 records), PARP1 (Proximity Label-MS; 3 records), RBPMS (Two-hybrid; 3 records), RNF2 (Affinity Capture-MS; 3 records), TMEM171 (Affinity Capture-MS; 3 records), ZNF428 (Affinity Capture-MS; 3 records)
SIGNOR signaling
2 signaling 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 86 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 | 12.9× | 2e-03 |
Disease & clinical
Genetic variants
Variant evidence for POGZ: 959 ClinVar records (204 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.
ClinVar
959 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 115 |
| Likely pathogenic | 89 |
| Uncertain significance | 400 |
| Likely benign | 169 |
| Benign | 58 |
Top pathogenic / likely-pathogenic (15)
Showing the 15 best-reviewed of 204 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.
| Variant ID | HGVS | Classification | Review | Submitters |
|---|---|---|---|---|
| 373048 | NM_015100.4(POGZ):c.1180_1181del (p.Met394fs) | Pathogenic | criteria provided, multiple submitters, no conflicts | 16 |
| 218149 | NM_015100.4(POGZ):c.2935C>T (p.Arg979Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 8 |
| 224724 | NM_015100.4(POGZ):c.3001C>T (p.Arg1001Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 6 |
| 280468 | NM_015100.4(POGZ):c.2350C>T (p.Arg784Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 5 |
| 218146 | NM_015100.4(POGZ):c.2321_2324del (p.Ser774fs) | Pathogenic | criteria provided, multiple submitters, no conflicts | 4 |
| 426598 | NM_015100.4(POGZ):c.3022C>T (p.Arg1008Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 4 |
| 620444 | NM_015100.4(POGZ):c.1522C>T (p.Arg508Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 4 |
| 987080 | NM_015100.4(POGZ):c.2092C>T (p.Arg698Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 4 |
| 451792 | NM_015100.4(POGZ):c.1608C>A (p.Tyr536Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 3 |
| 559853 | NM_015100.4(POGZ):c.2646_2647del (p.Asn882fs) | Pathogenic | criteria provided, multiple submitters, no conflicts | 3 |
| 620406 | NM_015100.4(POGZ):c.712C>T (p.Arg238Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 3 |
| 978966 | NM_015100.4(POGZ):c.2310C>G (p.Tyr770Ter) | Pathogenic | criteria provided, multiple submitters, no conflicts | 3 |
| 1032656 | NM_015100.4(POGZ):c.2768dup (p.His923fs) | Pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 1184127 | NM_015100.4(POGZ):c.3312del (p.Phe1104fs) | Pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 1705564 | NM_015100.4(POGZ):c.2709del (p.Pro903_Leu904insTer) | Pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
Per-variant reference — Sugi Variant
Explore POGZ’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,159):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 1:151406465–151406466 | acceptor_loss | 1.0000 | 2 |
| 1:151406909–151406910 | donor_loss | 1.0000 | 5 |
| 1:151407024–151407025 | acceptor_loss | 1.0000 | 4 |
| 1:151408099 | donor_loss | 1.0000 | 2 |
| 1:151408241–151408242 | acceptor_loss | 1.0000 | 3 |
| 1:151408243 | acceptor_gain | 1.0000 | |
| 1:151408413 | donor_gain | 1.0000 | |
| 1:151408692–151408693 | donor_loss | 1.0000 | 5 |
| 1:151408829–151408830 | acceptor_loss | 1.0000 | 5 |
| 1:151408834 | acceptor_gain | 1.0000 |
AlphaMissense
3,800 missense substitutions predicted likely pathogenic (of 9,223 scored), across 832 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| M790 | 9 | 0.998 | 1.000 |
| M579 | 9 | 0.996 | 1.000 |
| M588 | 9 | 0.996 | 1.000 |
| M510 | 9 | 0.988 | 0.999 |
| M8 | 9 | 0.958 | 0.998 |
| M467 | 9 | 0.957 | 0.999 |
| M830 | 9 | 0.950 | 0.999 |
| M513 | 9 | 0.910 | 0.998 |
| M394 | 9 | 0.859 | 0.982 |
| H512 | 8 | 1.000 | 1.000 |
| H516 | 8 | 1.000 | 1.000 |
| H548 | 8 | 1.000 | 1.000 |
| H583 | 8 | 1.000 | 1.000 |
| H766 | 8 | 1.000 | 1.000 |
| H789 | 8 | 1.000 | 1.000 |
| H794 | 8 | 1.000 | 1.000 |
| H553 | 8 | 0.999 | 1.000 |
| H578 | 8 | 0.999 | 1.000 |
| H608 | 8 | 0.999 | 1.000 |
| H613 | 8 | 0.999 | 1.000 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Disease associations
OMIM: gene MIM:614787 | disease phenotypes: MIM:616364, MIM:160700
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome | Definitive | Autosomal dominant | 5 |
ClinGen Gene-Disease Validity
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
1 validity classifications:
| Disease | Classification | Inheritance |
|---|---|---|
| intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome | Definitive | AD |
Genomics England panels (PanelApp)
Clinical diagnostic gene panels including this gene (8 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.
8 panels:
| Panel | Rating |
|---|---|
| DDG2P | green |
| Fetal anomalies | green |
| Hypotonic infant | green |
| Intellectual disability | green |
| Leukodystrophy, childhood onset | green |
| Severe microcephaly | green |
| Clefting | amber |
| Paediatric disorders | amber |
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
showing 60 of 161 phenotypes (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 |
| HP:0000369 | Low-set ears |
| HP:0000396 | Overfolded helix |
| HP:0000403 | Recurrent otitis media |
| HP:0000407 | Sensorineural hearing impairment |
| HP:0000437 | Depressed nasal tip |
| HP:0000447 | Pear-shaped nose |
| HP:0000455 | Broad nasal tip |
| HP:0000470 | Short neck |
| HP:0000483 | Astigmatism |
| HP:0000486 | Strabismus |
| HP:0000494 | Downslanted palpebral fissures |
| HP:0000505 | Visual impairment |
| HP:0000508 | Ptosis |
| HP:0000510 | Rod-cone dystrophy |
| HP:0000512 | Abnormal electroretinogram |
| HP:0000540 | Hypermetropia |
| HP:0000545 | Myopia |
| HP:0000577 | Exotropia |
| HP:0000582 | Upslanted palpebral fissure |
| HP:0000589 | Coloboma |
| HP:0000609 | Optic nerve hypoplasia |
| HP:0000612 | Iris coloboma |
| HP:0000618 | Blindness |
| HP:0000639 | Nystagmus |
| HP:0000648 | Optic atrophy |
| HP:0000649 | Abnormality of visual evoked potentials |
| HP:0000718 | Aggressive behavior |
| HP:0000722 | Compulsive behaviors |
| HP:0000729 | Autistic behavior |
| HP:0000733 | Motor stereotypy |
GWAS associations
4 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST002041_2 | Blood trace element (Cu levels) | 3e-20 |
| GCST005951_48 | Body mass index | 4e-9 |
| GCST007269_175 | Pulse pressure | 4e-8 |
| GCST010397_41 | Gut microbiota (bacterial taxa, rank normal transformation method) | 2e-6 |
EFO canonical traits (from GWAS)
4 canonical traits:
| 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 disease descriptors:
| 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 (CPIC guideline: no)
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 expression, increases abundance, affects cotreatment | 2 |
| Cadmium Chloride | increases abundance, decreases expression | 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 | decreases expression, affects cotreatment | 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)
Via MONDO — disease-level, not drug-specific.
showing 60 of 299 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05657860 | Phase 4 | COMPLETED | Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome |
| NCT05744479 | Phase 4 | RECRUITING | Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability |
| NCT06107829 | Phase 4 | WITHDRAWN | Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities |
| NCT06997198 | Phase 4 | RECRUITING | Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities |
| NCT04586348 | Phase 4 | UNKNOWN | Prenatal Iodine Supplementation and Early Childhood Neurodevelopment |
| NCT04873115 | Phase 4 | 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 | Phase 3 | 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 | Phase 3 | COMPLETED | Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants |
| NCT02757079 | Phase 3 | COMPLETED | Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders |
| NCT06915480 | Phase 3 | RECRUITING | Reducing Missed Appointments |
| NCT07377032 | Phase 3 | RECRUITING | TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders |
| NCT02304302 | Phase 2 | COMPLETED | Down Syndrome Memantine Follow-up Study |
| NCT03862950 | Phase 2 | COMPLETED | A Trial of Metformin in Individuals With Fragile X Syndrome (Met) |
| NCT04529226 | Phase 2 | UNKNOWN | Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis |
| NCT04821856 | Phase 2 | COMPLETED | Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability |
| NCT02909959 | Phase 2 | COMPLETED | Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder |
| NCT06081348 | Phase 2 | RECRUITING | Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders |
| NCT06352372 | Phase 2 | COMPLETED | Safety and Efficacy of tPBM for Epileptiform Activity in Autism |
| NCT05273320 | Phase 1 | COMPLETED | Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities |
| NCT05301361 | Phase 1 | ENROLLING_BY_INVITATION | Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities |
| NCT06016764 | Phase 1 | COMPLETED | Use of MRI and cTBS for Catatonia in Autism |
| NCT06586827 | Phase 1 | COMPLETED | Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD |
| NCT07531940 | Phase 1 | NOT_YET_RECRUITING | Escalating Doses of Memantine in Down Syndrome (MEDS-123) |
| NCT00503191 | Phase 1 | COMPLETED | NeuroModulation Technique Treatment of Autism |
| NCT04475848 | Phase 1 | COMPLETED | A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants |
| NCT06300398 | Phase 1 | COMPLETED | IAMA-6 Oral Dose Study in Healthy Adults |
| NCT03479476 | Phase 2/3 | COMPLETED | A Trial of Metformin in Individuals With Fragile X Syndrome |
| NCT02616796 | Phase 1/2 | COMPLETED | Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome |
| NCT06860672 | Early Phase 1 | TERMINATED | 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 |
| NCT02451761 | Not specified | COMPLETED | Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability |
| NCT02461420 | Not specified | ACTIVE_NOT_RECRUITING | Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome |
| NCT02461459 | Not specified | ACTIVE_NOT_RECRUITING | Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC) |
| NCT02486081 | Not specified | COMPLETED | Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population |
| NCT02504502 | Not specified | COMPLETED | Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients |
| NCT02513277 | Not specified | COMPLETED | Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study |
| NCT02561754 | Not specified | COMPLETED | Weight Management for Adolescents With IDD |
| NCT02591446 | Not specified | COMPLETED | Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders |
| NCT02714868 | Not specified | COMPLETED | Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications) |
| NCT02721394 | Not specified | UNKNOWN | FCT With Young Children With ID in the UK: A Feasibility Project V.1 |
| NCT02746614 | Not specified | COMPLETED | Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability |
| NCT02836405 | Not specified | COMPLETED | TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders |
| NCT02862808 | Not specified | COMPLETED | Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study |
| NCT02881333 | Not specified | UNKNOWN | Various Type of Genetic Events in Patients With Intellectual Disability |
| NCT02889068 | Not specified | COMPLETED | Targeted Next Generation Sequencing and Intellectual Disability |
| NCT02914951 | Not specified | ENROLLING_BY_INVITATION | Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability |
| NCT02919826 | Not specified | COMPLETED | Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities |
| NCT02934854 | Not specified | WITHDRAWN | Biomarker for Creatine Deficiency Syndromes (BioCDS) |
| NCT03033797 | Not specified | UNKNOWN | Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities |
| NCT03135236 | Not specified | COMPLETED | Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome |
Related Atlas pages
- Associated diseases: intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): hearing loss disorder, hypothyroidism, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, myopia, sensorineural hearing loss disorder, strabismus