ROGDI

Chr 16AR

rogdi atypical leucine zipper

Also known as: KTZS, RAV2, ROGD1

NCBI Gene: 79641ENSG00000067836UniProt: Q9GZN7

Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Kohlschutter-Tonz syndromeMIM #226750
AR
UniProtKohlschuetter-Toenz syndrome
577
ClinVar variants
67
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ROGDI
🧬
Gene-Disease Validity (ClinGen)
amelocerebrohypohidrotic syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 197 VUS of 577 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.42LOEUF
pLI 0.000
Z-score 0.32
OE 0.91 (0.60–1.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.32Z-score
OE missense 1.29 (1.15–1.45)
212 obs / 164.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.91 (0.60–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.29 (1.15–1.45)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.66
0≤1.21.6
LoF obs/exp: 14 / 15.4Missense obs/exp: 212 / 164.3Syn Z: -4.35

ClinVar Variant Classifications

577 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic16
VUS197
Likely Benign275
Benign24
Conflicting14
51
Pathogenic
16
Likely Pathogenic
197
VUS
275
Likely Benign
24
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
40
0
51
Likely Pathogenic
12
0
4
0
16
VUS
1
151
44
1
197
Likely Benign
0
2
149
124
275
Benign
0
1
18
5
24
Conflicting
—14
Total24154255130577

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ROGDI · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ROGDI-related Kohlschutter-Tonz syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Kohlschutter-Tonz syndrome

MIM #226750

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ROGDI
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Perampanel effectiveness in treating ROGDI-related Kohlschütter-Tönz syndrome: first reported case in China and literature review.
Meng L et al.·BMC Med Genomics
2023Review
ROGDI-Related Disorder Resulting from Disruption of Complex Interactive Neuro-Dental Developmental Networks: A Review and Description of the First Missense Variant.
Gverdtsiteli S et al.·Genes (Basel)
2025Review
Kohlschütter-Tönz syndrome: Case report with novel feature and detailed review of features associated with ROGDI variants.
Liepina L et al.·Am J Med Genet A
2022Review
SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome.
Schossig A et al.·J Med Genet
2017Clinical trial
Transcript Long-Read Sequencing Unveils the Molecular Complexity of a Novel ROGDI Splicing Variant in a Tunisian Family With Kohlschütter-Tönz Syndrome.
Essid M et al.·Clin Genet
2025Case report
The Kohlschütter-Tönz syndrome associated gene Rogdi encodes a novel presynaptic protein.
Riemann D et al.·Sci Rep
2017
Kohlschütter-Tönz syndrome: mutations in ROGDI and evidence of genetic heterogeneity.
Tucci A et al.·Hum Mutat
2013
A novel ROGDI gene mutation is associated with Kohlschutter-Tonz syndrome.
Aswath N et al.·Oral Surg Oral Med Oral Pathol Oral Radiol
2018Case report
Genotype-based databases for variants causing rare diseases.
Lanthaler B et al.·Gene
2014
Epileptic encephalopathy and amelogenesis imperfecta: Kohlschütter-Tönz syndrome.
Schossig A et al.·Eur J Med Genet
2012Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Citrate Transporter DeficiencyEpilepsyRare Diseases

SLC13A5 Deficiency Natural History Study - Remote Only

ENROLLING BY INVITATION
NCT04681781TESS Research FoundationStarted 2021-03-01

External Resources

Links to major genomics databases and tools