POGZ

pogo transposable element derived with ZNF domain, the group of Helix-turn-helix CENPB type domain containing|DNA transposon derived genes

Basic information

Region (hg38): 1:151402723-151459494

Links

ENSG00000143442 ∙ NCBI:23126 ∙ OMIM:614787 ∙ HGNC:18801 ∙ Uniprot:Q7Z3K3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (Strong), mode of inheritance: AD
• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (Definitive), mode of inheritance: AD
• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (Supportive), mode of inheritance: AD
• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
White-Sutton syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	25533962; 26739615

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POGZ gene.

• not provided (309 variants)
• Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (166 variants)
• Inborn genetic diseases (154 variants)
• POGZ-related condition (15 variants)
• Autism spectrum disorder (10 variants)
• Intellectual disability (9 variants)
• not specified (6 variants)
• Neurodevelopmental disorder (5 variants)
• See cases (4 variants)
• dysmorphy;intellectual deficiency (1 variants)
• 17 conditions (1 variants)
• Smith-Magenis Syndrome-like (1 variants)
• POGZ-Related Disorder (1 variants)
• Global developmental delay;Speech apraxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POGZ gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	62	9	73
missense	2	9	181	36	3	231
nonsense	22	12	2			36
start loss						0
frameshift	40	32	3			75
inframe indel			6	1		7
splice donor/acceptor (+/-2bp)	5	4	5			14
splice region	1	2	8	5	2	18
non coding	1		1	17	48	67
Total	70	57	200	116	60

Highest pathogenic variant AF is 0.00000657

Variants in POGZ

This is a list of pathogenic ClinVar variants found in the POGZ region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-151404532-TA-T			Likely benign (Aug 12, 2019)
1-151404772-T-C		Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Benign (Oct 25, 2021)
1-151404805-A-T		Inborn genetic diseases	Likely benign (Jan 19, 2018)
1-151404816-G-T		Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Likely benign (Aug 17, 2023)
1-151404828-C-T		Autism spectrum disorder	association (-)
1-151404829-T-A		Inborn genetic diseases • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Benign/Likely benign (Apr 11, 2023)
1-151404833-T-A		Inborn genetic diseases • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Conflicting classifications of pathogenicity (Aug 01, 2022)
1-151404838-G-A			Likely benign (Jun 23, 2018)
1-151404852-C-T			Uncertain significance (Sep 20, 2022)
1-151404870-C-G		Inborn genetic diseases • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Uncertain significance (Apr 11, 2023)
1-151404881-T-C		Inborn genetic diseases	Uncertain significance (May 09, 2017)
1-151404887-C-T		not specified	Uncertain significance (Jan 30, 2024)
1-151404900-T-C		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 11, 2023)
1-151404903-T-G		Autism spectrum disorder	association (-)
1-151404914-G-C			Likely benign (Feb 02, 2023)
1-151404927-G-A			Uncertain significance (Feb 11, 2020)
1-151404931-A-C		Inborn genetic diseases • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Benign (Apr 11, 2023)
1-151404931-A-T		Inborn genetic diseases • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Benign/Likely benign (Apr 11, 2023)
1-151404931-AG-CT		Inborn genetic diseases	Uncertain significance (May 08, 2017)
1-151404932-G-T		Inborn genetic diseases	Uncertain significance (Jan 10, 2017)
1-151404933-T-A			Uncertain significance (Jun 24, 2019)
1-151404940-C-A		Inborn genetic diseases • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Benign (Apr 11, 2023)
1-151404943-A-C		Inborn genetic diseases	Likely benign (Dec 22, 2018)
1-151404946-A-C		Autism spectrum disorder • Inborn genetic diseases • POGZ-related disorder • Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	Benign/Likely benign (Mar 01, 2024)
1-151404947-T-C		Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POGZ	protein_coding	protein_coding	ENST00000271715	18	56742

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.95e-9	125740	0	5	125745	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.51	522	801	0.651	0.0000447	9188
Missense in Polyphen		203	375.17	0.54109		4367
Synonymous	0.403	294	303	0.971	0.0000165	2910
Loss of Function	7.15	3	65.4	0.0459	0.00000418	650

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000155	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:20562864}.
• Disease: DISEASE: Note=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). {ECO:0000269|PubMed:25694107}.; DISEASE: White-Sutton syndrome (WHSUS) [MIM:616364]: A mental retardation syndrome characterized by developmental delay, intellectual disability, hypotonia, behavioral abnormalities, and dysmorphic facial features. Variable features include short stature, microcephaly, strabismus and hearing loss. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:26739615}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.128
• rvis_EVS: -1.53
• rvis_percentile_EVS: 3.41

Haploinsufficiency Scores

• pHI: 0.239
• hipred: Y
• hipred_score: 0.775
• ghis: 0.701

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pogz

Zebrafish Information Network

• Gene name: pogza
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;mitotic sister chromatid cohesion;regulation of gene expression;cell division;kinetochore assembly
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;cytosol;histone methyltransferase complex
• Molecular function: RNA polymerase II core promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;metal ion binding