RTTN

rotatin, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 18:70003031-70205726

Links

ENSG00000176225 ∙ NCBI:25914 ∙ OMIM:610436 ∙ HGNC:18654 ∙ Uniprot:Q86VV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephalic primordial dwarfism due to RTTN deficiency (Definitive), mode of inheritance: AR
• microcephalic primordial dwarfism due to RTTN deficiency (Strong), mode of inheritance: AR
• microcephalic primordial dwarfism due to RTTN deficiency (Supportive), mode of inheritance: AR
• microcephalic primordial dwarfism due to RTTN deficiency (Strong), mode of inheritance: AR
• microcephalic primordial dwarfism due to RTTN deficiency (Definitive), mode of inheritance: AR
• bilateral generalized polymicrogyria (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, short stature, and polymicrogyria with or without seizures	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	Musculoskeletal; Neurologic	22939636; 26608784

ClinVar

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

• not_provided (1157 variants)
• Inborn_genetic_diseases (313 variants)
• not_specified (91 variants)
• RTTN-related_disorder (78 variants)
• Microcephalic_primordial_dwarfism_due_to_RTTN_deficiency (76 variants)
• MICROCEPHALY,_SHORT_STATURE,_AND_POLYMICROGYRIA_WITH_SEIZURES (4 variants)
• Primary_microcephaly (4 variants)
• Microcephaly (3 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RTTN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000173630.4. 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			15	288	10	313
missense	2	9	595	46	9	661
nonsense	20	12	1			33
start loss			1			1
frameshift	17	4	1			22
splice donor/acceptor (+/-2bp)	1	19	5			25
Total	40	44	618	334	19

Highest pathogenic variant AF is 0.000056998837

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RTTN	protein_coding	protein_coding	ENST00000255674	49	202153

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124628	0	169	124797	0.000677

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.107	1124	1.13e+3	0.991	0.0000570	14469
Missense in Polyphen		301	371.76	0.80966		4995
Synonymous	-0.438	446	434	1.03	0.0000229	4369
Loss of Function	3.97	73	120	0.608	0.00000637	1477

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00134	0.00127
Ashkenazi Jewish	0.000400	0.000397
East Asian	0.00101	0.00100
Finnish	0.000419	0.000417
European (Non-Finnish)	0.000708	0.000698
Middle Eastern	0.00101	0.00100
South Asian	0.000634	0.000621
Other	0.00104	0.000990

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the genetic cascade that governs left-right specification. Plays a role in the maintenance of a normal ciliary structure. Required for correct asymmetric expression of NODAL, LEFTY and PITX2. {ECO:0000269|PubMed:22939636}.
• Disease: DISEASE: Microcephaly, short stature, and polymicrogyria with or without seizures (MSSP) [MIM:614833]: A disease characterized by many irregular small gyri in the brain surface and fusion of the molecular layer over multiple small gyri, which gives a festooned appearance to the cortical surface, without abnormal neuronal migration. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. MSSP patients have moderate to severe mental retardation, poor speech, dysarthria and seizures. {ECO:0000269|PubMed:22939636}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.931
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.28

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.550

Gene Damage Prediction

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

Gene ontology

• Biological process: centriole replication;determination of left/right symmetry;centriole-centriole cohesion;ciliary basal body organization
• Cellular component: centrosome;centriole;ciliary basal body