SETD5

SET domain containing 5, the group of SET domain containing

Basic information

Region (hg38): 3:9397615-9479240

Links

ENSG00000168137 ∙ NCBI:55209 ∙ OMIM:615743 ∙ HGNC:25566 ∙ Uniprot:Q9C0A6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (Strong), mode of inheritance: AD
• intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (Supportive), mode of inheritance: AD
• intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (Strong), mode of inheritance: AD
• intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 23	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	Craniofacial; Musculoskeletal; Neurologic	24680889

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SETD5 gene.

• not_provided (1083 variants)
• Intellectual_disability-facial_dysmorphism_syndrome_due_to_SETD5_haploinsufficiency (230 variants)
• Inborn_genetic_diseases (195 variants)
• SETD5-related_disorder (65 variants)
• not_specified (48 variants)
• Intellectual_disability (10 variants)
• See_cases (8 variants)
• Neurodevelopmental_disorder (3 variants)
• Moyamoya_angiopathy_with_developmental_delay (3 variants)
• Developmental_disorder (3 variants)
• Rare_genetic_intellectual_disability (2 variants)
• Neurodevelopmental_abnormality (2 variants)
• KBG_syndrome (2 variants)
• Cleft_lip (1 variants)
• SETD5-related_syndromic_intellectual_disability (1 variants)
• Syndromic_intellectual_disability (1 variants)
• Autism_spectrum_disorder (1 variants)
• Microcephaly (1 variants)
• Chromatinopathy (1 variants)
• NK-cell_enteropathy (1 variants)
• Polymicrogyria (1 variants)
• Global_developmental_delay (1 variants)
• Neurodevelopmental_delay (1 variants)
• Hearing_impairment (1 variants)
• Hyperphosphatasia_with_intellectual_disability_syndrome_4 (1 variants)
• Cleft_palate (1 variants)
• Non-syndromic_intellectual_disability (1 variants)
• Heart,_malformation_of (1 variants)
• Cornelia_de_Lange-like_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SETD5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001080517.3. 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		2	12	181	22	217
missense	7	26	544	154	6	737
nonsense	49	23	5	1		78
start loss						0
frameshift	107	38	12	1		158
splice donor/acceptor (+/-2bp)	12	18	8			38
Total	175	107	581	337	28

Highest pathogenic variant AF is 0.000006369896

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SETD5	protein_coding	protein_coding	ENST00000402198	21	81626

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124610	0	32	124642	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	683	772	0.885	0.0000430	9258
Missense in Polyphen		177	311.9	0.56748		3567
Synonymous	-0.684	296	281	1.05	0.0000144	2959
Loss of Function	6.70	9	69.1	0.130	0.00000434	803

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00106	0.00106
Ashkenazi Jewish	0.000201	0.000199
East Asian	0.000111	0.000111
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000355	0.0000354
Middle Eastern	0.000111	0.000111
South Asian	0.000132	0.000131
Other	0.000333	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transcriptional regulator that acts via the formation of large multiprotein complexes that modify and/or remodel the chromatin. Acts as a regulator of histone acetylation during gene transcription. {ECO:0000250|UniProtKB:Q5XJV7}.
• Disease: DISEASE: Mental retardation, autosomal dominant 23 (MRD23) [MIM:615761]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD23 patients manifest moderate to severe intellectual disability with additional variable features of brachycephaly, a low hairline, depressed nasal bridge, prominent high nasal root, tubular nose, upslanting palpebral fissures, long and smooth philtrum, micrognathia, thin upper lip, and crowded teeth. Behavioral problems, including obsessive-compulsive disorder, hand flapping with ritualized behavior, and autism, are prominent features. {ECO:0000269|PubMed:24680889, ECO:0000269|PubMed:25138099, ECO:0000269|PubMed:27375234, ECO:0000269|PubMed:28549204}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Histone Modifications (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.0174
• rvis_EVS: -0.79
• rvis_percentile_EVS: 12.6

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.797

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: setd5
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: covalent chromatin modification;regulation of histone acetylation;regulation of chromatin organization
• Cellular component: nucleus;nucleoplasm;Cdc73/Paf1 complex