ADD3

adducin 3, the group of Adducin family

Basic information

Region (hg38): 10:109996367-110135565

Previous symbols: [ "ADDL" ]

Links

ENSG00000148700 ∙ NCBI:120 ∙ OMIM:601568 ∙ HGNC:245 ∙ Uniprot:Q9UEY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebral palsy, spastic quadriplegic, 3 (Limited), mode of inheritance: AR
• spastic quadriplegic cerebral palsy (Supportive), mode of inheritance: AR
• cerebral palsy, spastic quadriplegic, 3 (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder with motor features (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebral palsy, spastic quadriplegic, 3	AR	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	Neurologic	23836506

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADD3 gene.

• not provided (139 variants)
• Inborn genetic diseases (25 variants)
• Cerebral palsy, spastic quadriplegic, 3 (3 variants)
• Cerebral palsy (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADD3 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				32	1	33
missense		1	86	6	2	95
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			3	6	1	10
non coding				9	3	12
Total	0	1	89	47	6

Variants in ADD3

This is a list of pathogenic ClinVar variants found in the ADD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-110100661-C-T		not specified	Uncertain significance (Jun 06, 2023)
10-110100668-C-T			Likely benign (Nov 06, 2022)
10-110100670-G-T		not specified	Uncertain significance (Jul 17, 2023)
10-110100674-A-C			Uncertain significance (Jul 06, 2022)
10-110100675-G-A			Uncertain significance (Dec 02, 2021)
10-110100677-C-T			Likely benign (Jan 22, 2024)
10-110100678-G-A			Uncertain significance (Dec 02, 2021)
10-110100695-T-G			Likely benign (Nov 06, 2022)
10-110100723-T-G		not specified	Uncertain significance (Apr 22, 2022)
10-110100732-C-T		not specified	Uncertain significance (Feb 22, 2023)
10-110100739-A-G			Uncertain significance (Mar 31, 2023)
10-110100774-A-G			Uncertain significance (Jun 26, 2023)
10-110100785-T-C			Likely benign (May 25, 2023)
10-110100800-C-T			Likely benign (Feb 26, 2018)
10-110100815-G-A			Likely benign (Jul 30, 2023)
10-110100823-G-A		not specified	Uncertain significance (Mar 02, 2023)
10-110100842-A-C		not specified	Uncertain significance (Oct 26, 2022)
10-110100844-G-T			Uncertain significance (Aug 04, 2023)
10-110100866-G-A			Likely benign (Jun 03, 2022)
10-110112760-A-G			Likely benign (Oct 24, 2022)
10-110112788-A-G			Likely benign (Jan 02, 2022)
10-110112794-G-A			Likely benign (May 22, 2023)
10-110112826-G-A		not specified	Uncertain significance (Dec 11, 2023)
10-110112837-A-G		not specified	Uncertain significance (Jan 23, 2024)
10-110112863-T-G			Uncertain significance (Nov 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADD3	protein_coding	protein_coding	ENST00000356080	14	139198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00120	125717	0	24	125741	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.330	363	381	0.952	0.0000191	4638
Missense in Polyphen		110	134.5	0.81785		1650
Synonymous	-0.103	135	133	1.01	0.00000684	1348
Loss of Function	5.04	4	37.2	0.108	0.00000207	430

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00108	0.00107
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin. {ECO:0000269|PubMed:23836506}.
• Disease: DISEASE: Cerebral palsy, spastic quadriplegic 3 (CPSQ3) [MIM:617008]: A form of cerebral palsy, a group of non-progressive disorders of movement and/or posture resulting from defects in the developing central nervous system. CPSQ3 is an autosomal recessive neurodevelopmental disorder characterized by variable spasticity and cognitive impairment. {ECO:0000269|PubMed:23836506}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.209
• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.82

Haploinsufficiency Scores

• pHI: 0.719
• hipred: N
• hipred_score: 0.465
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.190

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Add3
• Phenotype: hematopoietic system phenotype; normal phenotype

Zebrafish Information Network

• Gene name: add3a
• Affected structure: intrahepatic bile duct
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: barbed-end actin filament capping;actin filament bundle assembly;transmembrane transport
• Cellular component: condensed nuclear chromosome;nucleoplasm;cytosol;cytoskeleton;plasma membrane;brush border;cell-cell junction;cell cortex;postsynaptic density;membrane;plasma membrane raft
• Molecular function: structural molecule activity;structural constituent of cytoskeleton;calmodulin binding;spectrin binding;actin filament binding