NKAP

NFKB activating protein

Basic information

Region (hg38): X:119920672-119943751

Links

ENSG00000101882 ∙ NCBI:79576 ∙ OMIM:300766 ∙ HGNC:29873 ∙ Uniprot:Q8N5F7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type (Moderate), mode of inheritance: XL
• intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type	XL	Cardiovascular	The condition can include cardiovascular anomalies, including valvular and other anomalies, and awareness may allow early detection (eg, via echocardiogram) and management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	26358559; 31587868

ClinVar

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

• Inborn_genetic_diseases (28 variants)
• not_provided (20 variants)
• Intellectual_developmental_disorder,_X-linked,_syndromic,_Hackmann-Di_Donato_type (15 variants)
• NKAP-related_disorder (5 variants)
• not_specified (2 variants)
• Global_developmental_delay (1 variants)
• Developmental_delay,_impaired_growth,_dysmorphic_facies,_and_axonal_neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NKAP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024528.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense	2	4	37	8		51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	4	37	9	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NKAP	protein_coding	protein_coding	ENST00000371410	9	18722

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00265	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	97	149	0.652	0.0000106	2668
Missense in Polyphen		32	37.244	0.8592		599
Synonymous	0.502	50	54.7	0.914	0.00000365	799
Loss of Function	3.87	0	17.4	0.00	0.00000155	295

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional repressor. Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development. Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter. {ECO:0000269|PubMed:14550261, ECO:0000269|PubMed:19409814}.

Recessive Scores

• pRec: 0.102

Intolerance Scores

• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.427
• hipred: Y
• hipred_score: 0.545
• ghis: 0.610

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.487

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nkap
• Phenotype: hematopoietic system phenotype; immune system phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: nkap
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: necrotic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;Notch signaling pathway;stem cell population maintenance;granulocyte differentiation;T cell differentiation in thymus;negative regulation of transcription, DNA-templated;positive regulation of alpha-beta T cell differentiation;hematopoietic stem cell proliferation
• Cellular component: nucleoplasm;cytosol
• Molecular function: chromatin binding;RNA binding;protein binding;chromatin DNA binding