SPDL1

spindle apparatus coiled-coil protein 1

Basic information

Region (hg38): 5:169583636-169604778

Previous symbols: [ "CCDC99" ]

Links

ENSG00000040275 ∙ NCBI:54908 ∙ OMIM:616401 ∙ HGNC:26010 ∙ Uniprot:Q96EA4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPDL1 gene.

• not_specified (83 variants)
• not_provided (6 variants)
• Severe_primary_microcephaly (1 variants)
• Neonatal_death (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPDL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017785.5. 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			80	4		84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)				1		1
Total	0	0	80	6	1

Highest pathogenic variant AF is 0.0000047919602

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPDL1	protein_coding	protein_coding	ENST00000265295	11	21145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.60e-17	0.116	125495	0	253	125748	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.236	324	312	1.04	0.0000163	3989
Missense in Polyphen		95	103.98	0.91361		1434
Synonymous	-1.08	123	109	1.13	0.00000536	1063
Loss of Function	1.12	29	36.3	0.800	0.00000213	429

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00145	0.00145
Ashkenazi Jewish	0.00486	0.00477
East Asian	0.000470	0.000435
Finnish	0.000372	0.000370
European (Non-Finnish)	0.00114	0.00112
Middle Eastern	0.000470	0.000435
South Asian	0.000662	0.000653
Other	0.00117	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the localization of dynein and dynactin to the mitotic kintochore. Dynein is believed to control the initial lateral interaction between the kinetochore and spindle microtubules and to facilitate the subsequent formation of end-on kinetochore-microtubule attachments mediated by the NDC80 complex. Also required for correct spindle orientation. Does not appear to be required for the removal of spindle assembly checkpoint (SAC) proteins from the kinetochore upon bipolar spindle attachment (PubMed:17576797, PubMed:19468067). Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (PubMed:25035494). {ECO:0000255|HAMAP-Rule:MF_03041, ECO:0000269|PubMed:17576797, ECO:0000269|PubMed:19468067, ECO:0000269|PubMed:25035494}.
• Pathway: Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.0826

Intolerance Scores

• rvis_EVS: 1.25
• rvis_percentile_EVS: 93.44

Haploinsufficiency Scores

• pHI: 0.121
• hipred: N
• hipred_score: 0.246
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spdl1

Gene ontology

• Biological process: establishment of mitotic spindle orientation;mitotic metaphase plate congression;mitotic spindle assembly checkpoint;protein localization to kinetochore;cell division
• Cellular component: spindle pole;condensed chromosome outer kinetochore;nucleus;microtubule organizing center;cytosol
• Molecular function: protein binding;enzyme binding;kinetochore binding