ZFPM2

zinc finger protein, FOG family member 2, the group of Zinc fingers C2H2-type|SET domain containing|PR/SET domain family|Zinc fingers C2HC-type

Basic information

Region (hg38): 8:104590732-105804539

Links

ENSG00000169946 ∙ NCBI:23414 ∙ OMIM:603693 ∙ HGNC:16700 ∙ Uniprot:Q8WW38 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diaphragmatic hernia 3 (Limited), mode of inheritance: AD
• tetralogy of fallot (Limited), mode of inheritance: AD
• 46,XY partial gonadal dysgenesis (Supportive), mode of inheritance: AD
• tetralogy of fallot (Strong), mode of inheritance: AD
• tetralogy of fallot (Limited), mode of inheritance: Unknown
• 46,XY sex reversal 9 (Strong), mode of inheritance: AD
• diaphragmatic hernia 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
46,XY sex reversal 9	AD	Oncologic	Individuals may be at risk for gonadal tumors, and awareness may allow preventive measures and early management	Cardiovascular; Genitourinary; Musculoskeletal; Neurologic; Pulmonary	14517948; 16103912; 17568391; 20807224; 24549039; 24702427; 25996639; 29018978; 29264446; 29536580; 31028076; 31962012

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFPM2 gene.

• 46,XY sex reversal 9 (173 variants)
• not provided (71 variants)
• Inborn genetic diseases (30 variants)
• not specified (26 variants)
• Diaphragmatic hernia 3 (10 variants)
• Tetralogy of Fallot (9 variants)
• ZFPM2-related condition (8 variants)
• 46,XY sex reversal 3 (8 variants)
• Double outlet right ventricle (2 variants)
• 46,XY sex reversal 9;Diaphragmatic hernia 3;Tetralogy of Fallot (1 variants)
• Diaphragmatic hernia 3;46,XY sex reversal 9;Tetralogy of Fallot (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFPM2 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	53	11	66
missense		1	120	22	5	148
nonsense	2	3	1			6
start loss						0
frameshift	2	2	1			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			1	3	5	9
non coding			1	4	11	16
Total	4	6	128	79	27

Highest pathogenic variant AF is 0.00000658

Variants in ZFPM2

This is a list of pathogenic ClinVar variants found in the ZFPM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-105318866-G-GGCGGCGGGA			Benign (Jun 19, 2021)
8-105318951-C-T		ZFPM2-related disorder	Likely pathogenic (Feb 23, 2024)
8-105318968-C-G			Likely benign (Mar 30, 2018)
8-105318992-G-C		46,XY sex reversal 9	Likely benign (Oct 06, 2023)
8-105318993-C-G		46,XY sex reversal 9 • Diaphragmatic hernia 3;Tetralogy of Fallot;46,XY sex reversal 9	Benign/Likely benign (Jan 16, 2024)
8-105419134-C-G		46,XY sex reversal 9	Benign (Nov 22, 2023)
8-105419140-C-A		46,XY sex reversal 9	Benign (Jun 27, 2023)
8-105419160-C-T		46,XY sex reversal 9	Likely benign (Sep 25, 2021)
8-105419175-A-G		46,XY sex reversal 9	Likely benign (Feb 01, 2020)
8-105419176-G-A			Uncertain significance (Oct 28, 2019)
8-105419177-A-G		46,XY sex reversal 9	Uncertain significance (Sep 01, 2021)
8-105419181-A-G		46,XY sex reversal 9	Likely benign (May 04, 2022)
8-105419192-A-G		Tetralogy of Fallot • Double outlet right ventricle • Diaphragmatic hernia 3 • 46,XY sex reversal 9 • 46,XY sex reversal 3 • not specified • ZFPM2-related disorder	Benign/Likely benign (Jan 21, 2024)
8-105419193-G-A		46,XY sex reversal 9	Likely benign (Aug 31, 2023)
8-105419224-C-G		46,XY sex reversal 9 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 01, 2023)
8-105419228-T-G			Uncertain significance (Oct 05, 2022)
8-105419233-G-A		Diaphragmatic hernia 3 • 46,XY sex reversal 9	Conflicting classifications of pathogenicity (May 23, 2023)
8-105419294-G-A		46,XY sex reversal 9	Benign (Aug 09, 2022)
8-105419295-T-G		46,XY sex reversal 9	Likely pathogenic (Oct 01, 2021)
8-105444272-T-G		46,XY sex reversal 9	Benign (Nov 05, 2021)
8-105444320-G-T		46,XY sex reversal 9	Likely benign (Jun 27, 2023)
8-105444321-G-A		46,XY sex reversal 9	Uncertain significance (Nov 27, 2023)
8-105444331-C-T		ZFPM2-related disorder	Uncertain significance (May 25, 2023)
8-105444338-A-G		46,XY sex reversal 9 • ZFPM2-related disorder	Benign/Likely benign (Nov 03, 2023)
8-105444341-G-A		46,XY sex reversal 9	Likely benign (Dec 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFPM2	protein_coding	protein_coding	ENST00000407775	8	485841

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000441	124639	0	10	124649	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.213	581	596	0.975	0.0000317	7616
Missense in Polyphen		220	241.06	0.91262		3051
Synonymous	0.216	220	224	0.982	0.0000128	2185
Loss of Function	5.82	2	43.3	0.0461	0.00000245	528

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000204	0.000204
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000559	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.00000895	0.00000885
Middle Eastern	0.0000559	0.0000556
South Asian	0.0000657	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA4, GATA5 and GATA6. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. Also required in gonadal differentiation, possibly be regulating expression of SRY. Probably acts a corepressor of NR2F2 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10438528}.
• Disease: DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. {ECO:0000269|PubMed:14517948, ECO:0000269|PubMed:20807224}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Diaphragmatic hernia 3 (DIH3) [MIM:610187]: Form of congenital diaphragmatic hernia (CDH). CDH refers to a group of congenital defects in the structural integrity of the diaphragm associated with often lethal pulmonary hypoplasia and pulmonary hypertension. {ECO:0000269|PubMed:16103912}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 46,XY sex reversal 9 (SRXY9) [MIM:616067]: A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females or have ambiguous external genitalia. {ECO:0000269|PubMed:24549039}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. {ECO:0000269|PubMed:20807224}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: MicroRNAs in cancer - Homo sapiens (human);Factors involved in megakaryocyte development and platelet production;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.264

Intolerance Scores

• loftool: 0.188
• rvis_EVS: 0.52
• rvis_percentile_EVS: 80.37

Haploinsufficiency Scores

• pHI: 0.562
• hipred: Y
• hipred_score: 0.738
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.911

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfpm2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;vasculogenesis;in utero embryonic development;outflow tract septum morphogenesis;right ventricular cardiac muscle tissue morphogenesis;gonadal mesoderm development;heart development;blood coagulation;lung development;negative regulation of fat cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic organ development;positive regulation of cardiac muscle cell proliferation;ventricular septum morphogenesis;negative regulation of cell death;positive regulation of male gonad development;negative regulation of female gonad development
• Cellular component: nucleus;nucleoplasm;cytoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;DNA binding;transcription coactivator activity;transcription corepressor activity;protein binding;transcription factor binding;zinc ion binding